Skip to main content

Advertisement

SpringerLink
Log in

Artemisinin and its derivatives: a promising cancer therapy

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The world is experiencing a cancer epidemic and an increase in the prevalence of the disease. Cancer remains a major killer, accounting for more than half a million deaths annually. There is a wide range of natural products that have the potential to treat this disease. One of these products is artemisinin; a natural product from Artemisia plant. The Nobel Prize for Medicine was awarded in 2015 for the discovery of artemisinin in recognition of the drug’s efficacy. Artemisinin produces highly reactive free radicals by the breakdown of two oxygen atoms that kill cancerous cells. These cells sequester iron and accumulate as much as 1000 times in comparison with normal cells. Generally, chemotherapy is toxic to both cancerous cells and normal cells, while no significant cytotoxicity from artemisinin to normal cells has been found in more than 4000 case studies, which makes it far different than conventional chemotherapy. The pleiotropic response of artemisinin in cancer cells is responsible for growth inhibition by multiple ways including inhibition of angiogenesis, apoptosis, cell cycle arrest, disruption of cell migration, and modulation of nuclear receptor responsiveness. It is very encouraging that artemisinin and its derivatives are anticipated to be a novel class of broad-spectrum antitumor agents based on efficacy and safety. This review aims to highlight these achievements and propose potential strategies to develop artemisinin and its derivatives as a new class of cancer therapeutic agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

AA:

Artemisinic Acid

A&D:

Artemisinin and its derivatives

ACTs:

Artemisinin based combination therapies

AN production:

Artemisinin production

CDK:

Cyclin-dependent kinase

MVA:

Cytosolic Mevalonate Pathway

DTP:

Developmental Therapeutics Program

DHAA:

Dihydroartemisinic Acid

DW:

Dry Weight

ERK:

Extracellular Signal-Regulated Kinases

MA:

Mevalonic Acid

NCI:

National Cancer Institute

TSTs:

Non-glandular T-shaped Trichomes

ROS:

Reactive Oxygen

SA:

Salicylic Acid

TFAR1:

Trichome-specific fatty acyl-CoA reductase 1

TDZ:

Thidiazuron

TAR1:

Trichome and artemisinin regulator 1

TAFR1:

Trichome-Specific Fatty Acyl-CoA Reductase 1

WHO:

World Health Organization

PLGA:

L-lactic-co-glycolic acid

References

  1. WHO (2008) Cancer statistics. WHO, Geneva

    Google Scholar 

  2. Hsiao WLW, Liu L (2010) The role of traditional Chinese herbal medicines in cancer therapy from TCM theory to mechanistic insights. Planta Med 76(11):1118–1131

    CAS  PubMed  Google Scholar 

  3. Hanahan D, Weinberg RA (2011) The hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  4. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar C et al (2001) The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767–773

    CAS  PubMed  Google Scholar 

  5. Efferth T, Saverbrey A, Olbrich A et al (2003) Molecular modes of action of artesunate in tumour cell lines. Mol Pharmacol 64(2):382–394

    CAS  PubMed  Google Scholar 

  6. Efferth T (2003) Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol 64(2):382–394

    CAS  PubMed  Google Scholar 

  7. Efferth T, Sauerbrey A, Olbrich A, Gebhart E, Rauch P, Weber HO et al (2003) Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol 64:382–394

    CAS  PubMed  Google Scholar 

  8. Reungpatthanaphong P, Mankhetkorn S (2002) Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biol Pharm Bull 25(12):1555–1561

    CAS  PubMed  Google Scholar 

  9. Woerdenbag HJ, Moskal TA, Pras N et al (1993) Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 56(6):849–856

    CAS  PubMed  Google Scholar 

  10. Dondorp AM, Nosten F, Yi P et al (2009) Artemisinin resistance in Plasmodium falciparum malaria. New Engl J Med 361(5):455–467

    CAS  PubMed  Google Scholar 

  11. Gordi T, Lepist EI (2004) Artemisinin derivatives: toxic for laboratory animals, safe for humans? Toxicol Lett 147(2):99–107

    CAS  PubMed  Google Scholar 

  12. Abad MJ, Bedoya LM, Apaza L, Bermejo P (2012) The Artemisia L. genus: a review of bioactive essential oils. Molecules 17(3):2542–2566

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Bora KS, Sharma A (2011) The genus Artemisia: a comprehensive review. Pharm Biol 49(1):101–109

    PubMed  Google Scholar 

  14. Sadiq A, Hayat MQ, Ashraf M (2014) Ethnopharmacology of Artemisia annua L.: A review. Artemisia annua-pharmacology and biotechnology. Springer, Cham, pp 9–25

    Google Scholar 

  15. Lubbe A, Seibert I, Klimkait T, Van der Kooy F (2012) Ethnopharmacology in overdrive: the remarkable anti-HIV activity of Artemisia annua. J Ethnopharmacol 141(3):854–859

    PubMed  Google Scholar 

  16. Lee SK, Kim H, Park J, Kim H-J, Kim KR, Son SH et al (2017) Artemisia annua extract prevents ovariectomy-induced bone loss by blocking receptor activator of nuclear factor kappa-B ligand-induced differentiation of osteoclasts. Sci Rep 7(1):17332

    PubMed  PubMed Central  Google Scholar 

  17. Li X, Ba Q, Liu Y, Yue Q, Chen P, Li J et al (2017) Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein. Cell Discov 3:17042

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Feng M-X, Hong J-X, Wang Q, Fan Y-Y, Yuan C-T, Lei X-H et al (2016) Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast cancer cells and osteoclasts. Sci Rep 6:19074

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen H, Sun B, Pan S, Jiang H, Sun X et al (2009) Dihydroartemisinin inhibits growth of pancreatic cancer cells in vitro and in vivo. Anticancer Drugs 20:131–140

    PubMed  Google Scholar 

  20. Chen T, Li M, Zhang R, Wang H et al (2009) Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy. J Cell Mol Med 13(7):1358–1370

    CAS  PubMed  Google Scholar 

  21. Kim SJ, Kim MS, Lee JW, Lee CH, Yoo H, Shin SH et al (2006) Dihydroartemisinin enhances radio sensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol 132:129–135

    CAS  PubMed  Google Scholar 

  22. Lu JJ, Chen S, Zhang M, Ding XW, Meng LH et al (2011) The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drugs 29:1276–1283

    CAS  PubMed  Google Scholar 

  23. Mu D, Chen W, Yu B, Zhang C, Zhang Y, Qi H et al (2008) Calcium and survivin are involved in the induction of apoptosis by dihydroartemisinin in human lung cancer SPC-A-1 cells. Methods Find Exp Clin Pharmacol 29:33–38

    Google Scholar 

  24. Singh NP, Lai H (2001) Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70:49–56

    CAS  PubMed  Google Scholar 

  25. Zhang Y, Xu G, Zhang S, Wang D, Prabha PS, Zuo Z (2018) Antitumor research on artemisinin and its bioactive derivatives. Nat Prod Bioprospect 8(4):303–319

    PubMed  PubMed Central  Google Scholar 

  26. Roth RJ, Acton N (1989) The isolation of sesquiterpenes from Artemisia annua. J Chem Educ 66:349–350

    CAS  Google Scholar 

  27. Brown TA (1993) Gene cloning and DNA analysis and introduction. In: Brown TA (ed), Blackwell Science, pp 139–144

  28. Nam W, Tak J, Ryu JK, Jung M, Yook JI, Kim HJ et al (2007) Effects of artemisinin and its derivatives on growth inhibition andapoptosis of oral cancer cells. Head Neck 29:335–340

    PubMed  Google Scholar 

  29. Posner GH, McRiner AJ, Paik IH, Sur S, Borstnik K, Xie S, Shapiro TA, Alagbala A, Foster B et al (2004) Anticancer and antimalarial efficacy and safety of artemisinin-derived trioxane dimers in rodents. J Med Chem 47:1299–1302

    CAS  PubMed  Google Scholar 

  30. Singh NP, Lai H (2004) Artemisinin induces apoptosis in human cancer cells. Anticancer Res 24:2277–2280

    CAS  PubMed  Google Scholar 

  31. Thomas E, Axel S, Armin O, Erich G, Pia R, Oliver W et al (2003) Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol 64:382–394

    Google Scholar 

  32. Wu GD, Zhou HJ, Wu XH et al (2006) Apoptosis of human umbilical vein endothelial cells induced by artesunate. Vasc Pharmacol 41(6):205–212

    Google Scholar 

  33. Chen HH, Zhou HJ, Wu GD, Lou XE et al (2004) Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1. Pharmacology 71:1–9

    CAS  PubMed  Google Scholar 

  34. Yamachika E, Habte T, Oda D et al (2004) Artemisinin: an alternative treatment for oral squamous cell carcinoma. Anticancer Res 24:2153–2160

    CAS  PubMed  Google Scholar 

  35. Jiao Y, Ge C, Meng Q, Cao J, Tong J, Fan S et al (2007) Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin 28(7):1045–1056. https://doi.org/10.1111/j.1745-7254.2007.00612.x

    Article  CAS  PubMed  Google Scholar 

  36. Disbrow GL, Baege AC, Kierpiec KA et al (2005) Dihydroartemisinin is Cytotoxic to papillomavirus-expressing epithelial cells in vitro and in vivo. Cancer Res 65:10854–10861

    CAS  PubMed  Google Scholar 

  37. Wu JM, Shan F, Wu GS, Li Y, Ding J, Xiao D, Han JX, Atassi G, Leonce S, Caignard DH, Renard P et al (2001) Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl group. Eur J Med Chem 36:469–479

    CAS  PubMed  Google Scholar 

  38. Efferth T, Olbrich A, Bauer R et al (2002) mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether. Biochem Pharmacol 64(4):617–623

    CAS  PubMed  Google Scholar 

  39. Sadava D, Phillips T, Lin C, Kane SE et al (2002) Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. Cancer Lett 179:151–156

    CAS  PubMed  Google Scholar 

  40. Efferth T, Benakis A, Romero MR, Tomicic M, Rauh R, Steinbach D et al (2004) Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radic Biol Med 37:998–1009

    CAS  PubMed  Google Scholar 

  41. Efferth T (2004) Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774. Biochem Pharmacol 67(9):1689–1700

    CAS  PubMed  Google Scholar 

  42. Firestone GL, Sundar SN (2009) Anticancer activities of artemisinin and its bioactive derivatives. Expert Rev Mol Med 11:32

    Google Scholar 

  43. O’Neill PM, Barton VE, Ward SA et al (2010) The molecular mechanism of action of artemisinin–the debate continues. Molecules 15:1705–1721

    PubMed  PubMed Central  Google Scholar 

  44. Henry L, Tomikazu S, Narendra PS et al (2005) Oncologic, endocrine and metabolic treatment of cancer with artemisinin and artemisinin tagged iron-carrying compounds. Expert Opin Ther Targets 9(5):995–1007

    Google Scholar 

  45. Rowen RJ (2002) Artemisinin: from malaria to cancer treatment. Townsend Lett Doct Patients 86–88

  46. Gong Y, Gallis BM, Goodlett DR, Yang Y, Lu H, Lacoste E et al (2013) Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines. Anticancer Res 33:123–132

    CAS  PubMed  Google Scholar 

  47. Krishna S, Bustamante L, Haynes RK, Staines HM et al (2008) Artemisinins: their growing importance in medicine. Trends Pharmacol Sci 29:520–527. https://doi.org/10.1016/j.tips.2008.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Paik IH, Xie S, Shapiro TA, Labonte T, Narducci Sarjeant AA, Baege AC et al (2006) Second generation, orally active, antimalarial, artemisinin-derived trioxane dimers with high stability, efficacy, and anticancer activity. JMedChem 49:2731–2734

    CAS  Google Scholar 

  49. Sertel S, Plinkert P, Efferth T et al (2013) Activity of artemisinin-type compounds against cancer cells. In: Wagner H, Ulrich-Merzenich G (eds) Evidence and rational based research on chinese drugs. Springer, Vienna, pp 333–362

    Google Scholar 

  50. Stockwin LH, Han B, Yu SX, Hollingshead MG, ElSohly MA, Gul W et al (2009) Artemisinin dimer anticancer activity correlates with heme-catalyzed reactive oxygen species generation and endoplasmic reticulum stress induction. Int J Cancer 125:1266–1275

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Yoon MK, Mitrea DM, Ou L, Kriwacki RW et al (2012) Cell cycle regulation by the intrinsically disordered proteins p21 and p27. Biochem Soc Trans 40:981–988

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Tin AS, Sundar SN, Tran KQ, Park AH, Poindexter KM, Firestone GL et al (2012) Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes. Anticancer Drugs 23:370–379

    CAS  PubMed  Google Scholar 

  53. Chen G, Gong R, Shi X, Yang D, Zhang G et al (2016) Halofuginone and artemisinin synergistically arrest cancer cells at the G1/G0 phase by upregulating p21Cip1 and p27Kip1. Oncotarget 7(31):50302–50314

    PubMed  PubMed Central  Google Scholar 

  54. Huang Z, Huang X, Jiang D, Zhang Y, Huang B, Luo G et al (2016) Dihydroartemisinin inhibits cell proliferation by induced G1 arrest and apoptosis in human nasopharyngeal carcinoma cells. J Cancer Res Ther 12(1):244–247. https://doi.org/10.4103/0973-1482.151855

    Article  CAS  PubMed  Google Scholar 

  55. Tong Y, Tong Y, Liu Y, Zheng H, Zheng L, Liu W, Wu J, Ou R, Zhang G, Li F, Hu M, Liu Z, Lu L et al (2016) Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling. Oncotarget 7(21):31413–31428

    PubMed  PubMed Central  Google Scholar 

  56. Hou J, Wang D, Zhang R, Wang H et al (2008) Experimental therapy of hepatoma with artemisinin and Its derivatives: In vitro and in vivo activity, chemosensitization, and mechanisms of action. Clin Cancer Res 14(17):5519–5530. https://doi.org/10.1158/1078-0432.CCR-08-0197

    Article  CAS  PubMed  Google Scholar 

  57. Willoughby JA, Sundar SN, Cheung M, Tin AS, Modiano J, Firestone GL et al (2009) Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression. J Biol Chem 284(4):2203–2213. https://doi.org/10.1074/jbc.M804491200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Steinbrück G, Pereira I, Efferth T et al (2010) Effects of artesunate on cytokinesis and G2/M cell cycle progression of tumour cells and budding yeast. Cancer Genom Proteom 7(6):337–346

    Google Scholar 

  59. Wang SJ, Gao Y, Chen H, Kong R, Jiang HC, Pan SH, Sun B et al (2010) Dihydroartemisinin inactivates NF-??B and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo. Cancer Lett 293(1):99–108. https://doi.org/10.1016/j.canlet.2010.01.001

    Article  CAS  PubMed  Google Scholar 

  60. K Liao, J Li, Z Wang et al (2014) Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells. Int J Clin Exp Pathol 7(12):8684–8691. Retrieved from www.ijcep.com

  61. Liao K, Li J, Wang Z et al (2014) Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells. Int J Clin Exp Pathol 7(12):8684–8691

    PubMed  PubMed Central  Google Scholar 

  62. Xu Q, Li Z-X, Peng H-Q, Sun Z-W, Cheng R-L, Ye Z-M, Li W-X (2011) Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo. J Zhejiang Univ Sci B 12(4):247–255  

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Ma H, Yao Q, Zhang AM, Lin S, Wang XX, Wu L, Chen ZT et al (2011) The effects of artesunate on the expression of EGFR and ABCG2 in A549 human lung cancer cells and a xenograft model. Molecules 16(12):10556–10569. https://doi.org/10.3390/molecules161210556

    Article  PubMed  PubMed Central  Google Scholar 

  64. Du W, Pang C, Xue Y, Zhang Q, Wei X et al (2015) Dihydroartemisinin inhibits the Raf/ERK/MEK and PI3K/AKT pathways in glioma cells. Oncol Lett. https://doi.org/10.3892/ol.2015.3699

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zhang J, Ling G, Xia Z, Fengyun D, Liqun L, Zuowang C, Yinghua X, Jiyong L, Qi X, Liu Ju et al (2016) Dihydroartemisinin induces endothelial cell anoikis through the activation of the JNK signaling pathway. Oncol Lett 12:1896–1900

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhao X, Zhong H, Wang R, Liu D, Waxman S, Zhao L, Jing Y et al (2015) Dihydroartemisinin and its derivative induce apoptosis in acute myeloid leukemia through Noxa-mediated pathway requiring iron and endoperoxide moiety. Oncotarget 6(8):5582–5596

    PubMed  PubMed Central  Google Scholar 

  67. Dong F (2014) Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis. Cancer Biol Ther 15(11):1479–1488

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Hwang YP, Yun HJ, Kim HG, Han EH, Lee GW, Jeong HG et al (2010) Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCα/Raf/MAPKs and NF-κB/AP-1-dependent mechanisms. Biochem Pharmacol 79(12):1714–1726

    CAS  PubMed  Google Scholar 

  69. Aung W, Sogawa C, Furukawa T, Saga T et al (2011) Anticancer effect of dihydroartemisinin (DHA) in a pancreatic tumor model evaluated by conventional methods and optical imaging. Anticancer Res 31:1549–1558

    CAS  PubMed  Google Scholar 

  70. He Q, Jingxue S, Xiao-Ling S, Jie A, Hong S, Lu W, Ying-Jie H, Qing S, Lin-Chun F, Saeed SM, Ying H et al (2010) Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells. Cancer Biol Ther 9(10):819–824

    CAS  PubMed  Google Scholar 

  71. Mao H (2013) Involvement of the mitochondrial pathway and Bim/Bcl-2 balance in dihydroartemisinin-induced apoptosis in human breast cancer in vitro. Int J Mol Med 31(1):213–218

    CAS  PubMed  Google Scholar 

  72. Wang JX, Tang W, Shi LP, Wan J, Zhou R, Ni J, Fu YF, Yang YF, Li Y, Zuo JP et al (2007) Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation. Br J Pharmacol 150:652–661

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Wu ZP, Gao CW, Wu YG, Zhu QS, Chen Y, Liu X, Liu C et al (2009) Inhibitive effect of artemether on tumor growth and angiogenesis in the rat C6 orthotopic brain gliomas model. Integr Cancer Ther 8:88–92

    PubMed  Google Scholar 

  74. Jiao Y, Tong J (2007) Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin 28(7):1045–1056

    CAS  PubMed  Google Scholar 

  75. Cheng R, Li C, Li C, Wei L, Li L, Zhang Y, Gao G et al (2013) The artemisinin derivative artesunate inhibits corneal neovascularization by inducing ROS-dependent apoptosis in vascular endothelial cells. Invest Ophthalmol Vis Sci 54(5):3400–3409

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Yang ND, Shi-Hao T, Shukie N, Yin S, Jing Z, Kevin S, Wei T, Wai-Shiu FW, Han-Ming S (2014) Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin. J Biol Chem 289(48):33425–33441

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Chen H, Shi L, Yang X, Li S, Guo X, Pan L et al (2010) Artesunate inhibiting angiogenesis induced by human myeloma RPMI8226 cells. Int J Hematol 92(4):587–597. https://doi.org/10.1007/s12185-010-0697-3

    Article  CAS  PubMed  Google Scholar 

  78. Chen H, Sun B, Wang S, Pan S, Gao Y, Bai X, Xue D et al (2010) Growth inhibitory effects of dihydroartemisinin on pancreatic cancer cells: involvement of cell cycle arrest and inactivation of nuclear factor-kappaB. J Cancer Res Clin Oncol 136(6):897–903

    CAS  PubMed  Google Scholar 

  79. Jia G, Rui K, Zhi-Bin M, Bing H, Yong-Wei W, Shang-Ha P, Ying-Hua L, Bei S et al (2014) The activation of c-Jun NH2-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells. J Exp Clin Cancer Res 33:8–15

    PubMed  PubMed Central  Google Scholar 

  80. Thomas S, Quinn BA, Das SK, Dash R, Emdad L, Dasgupta S et al (2013) Targeting the Bcl-2 family for cancer therapy. Exp Opin Ther Targets 17:61–75

    CAS  Google Scholar 

  81. Chen Y, Zhang D, Liao Z et al (2015) Anti-oxidant polydatin (piceid) protects against substantia nigral motor degeneration in multiple rodent models of parkinson’s disease. Mol Neurodegener 10:4

    PubMed  PubMed Central  Google Scholar 

  82. Morrissey C, Gallis B, Solazzi JW, Kim BJ, Gulati R, Vakar-Lopez F, Sasaki T (2010) Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells. Anticancer Drugs 21(4):423

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Mizushima N, Levine B, Cuervo AM, Klionsky DJ et al (2008) Autophagy fights disease through cellular self-digestion. Nature 451(7182):1069–1075

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Chen SS, Hu W, Wang Z, Lou XE, Zhou HJ et al (2015) p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy. Cancer Biol Ther. https://doi.org/10.1080/15384047.2015.1026477

    Article  PubMed  PubMed Central  Google Scholar 

  85. Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, Kroemer G et al (2015) Autophagy in malignant transformation and cancer progression. EMBO J 34(7):856–880. https://doi.org/10.15252/embj.201490784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Chen K, Shou L-M, Lin F, Duan W-M, Wu M-Y, Xie X, Tao M et al (2014) Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells. Anticancer Drugs 25:652–662

    PubMed  Google Scholar 

  87. Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X et al (2016) Ferroptosis is an autophagic cell death process. Cell Res 26(9):1021–1032. https://doi.org/10.1038/cr.2016.95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Li Z (2016) Artemisinin and its derivatives as a repurposing anticancer agent: what else do we need to do? Molecules 21(10):1331–1339

    PubMed Central  Google Scholar 

  89. Wong YK, He Y, Wang J, Xu C, Kalesh KA, Shen H, Wong WSF et al (2017) Artemisinin as an anticancer drug: recent advances in target profiling and mechanisms of action. Med Res Rev 2017(37):1492–1517. https://doi.org/10.1002/med.21446

    Article  CAS  Google Scholar 

  90. Giuliano S, Pagès G (2013) Mechanisms of resistance to anti-angiogenesis therapies. Biochimie 95(6):1110–1119. https://doi.org/10.1016/j.biochi.2013.03.002

    Article  CAS  PubMed  Google Scholar 

  91. Wang SJ, Sun B, Cheng ZX, Zhou HX, Gao Y, Kong R, Bai XW et al (2011) Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-??B pathway. Cancer Chemother Pharmacol 68(6):1421–1430. https://doi.org/10.1007/s00280-011-1643-7

    Article  CAS  PubMed  Google Scholar 

  92. Boyeva SA, Brezhneva TA, Maltseva AA, Buzlama AV, Slivkin AI (2007) Saponins of the Polemonium caeruleum L. and Beta vulgaris L. plants. The features of obtaining, the comparative assessment of the hypoglycemic activity. Proc Voronezh State Univ Chem Biol Pharm 1:139–141

    Google Scholar 

  93. Cavallo F, De Giovanni C, Nanni P, Forni G, Lollini P-L (2011) 2011: the immune hallmarks of cancer. Cancer Immunol Immunother 60(3):319–326

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Efferth T, Albini A, Pfeffer U et al (2006) Microarray expression profiles of angiogenesis-related genes predicttumor cell response to artemisinins. Pharmacogenom J 6:269–278

    Google Scholar 

  95. Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F, Lisanti MP et al (2017) Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol 14(1):11–31. https://doi.org/10.1038/nrclinonc.2016.60

    Article  CAS  PubMed  Google Scholar 

  96. Mi Y, Geng G, Zou Z, Gao J, Luo X, Liu Y et al (2015) Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells. PLoS ONE 10(3):1–21. https://doi.org/10.1371/journal.pone.0120426

    Article  CAS  Google Scholar 

  97. Ravindra KC, Ho WE, Cheng C, Godoy LC, Wishnok JS, Ong CN, Wong WS, Wogan GN, Tannenbaum SR et al (2015) Untargeted proteomics and systems-based mechanistic investigation of artesunate in human bronchial epithelial cells. Chem Res Toxicol 28(10):1903–1913

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Zhou Y, Weichao L, Xiao Y et al (2016) Profiling of Multiple Targets of Artemisinin Activated by Hemin in Cancer Cell Proteome. ACS Chem Biol 11:882–888. https://doi.org/10.1021/acschembio.5b01043

    Article  CAS  PubMed  Google Scholar 

  99. Li Y (2012) Qinghaosu (artemisinin): chemistry and pharmacology. Acta Pharmacol Sin 33:1141–1146. https://doi.org/10.1038/aps.2012.104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ho WE, Peh HY, Chan TK, Wong WS et al (2014) Artemisinin: pharmacological actions beyond anti-malarial. Pharmacol Ther 142:126–139. https://doi.org/10.1016/j.pharmthera.2013.12.001

    Article  CAS  PubMed  Google Scholar 

  101. Crespo-Ortiz MP, Wei MQ (2012) Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. J Biomed Biotechnol 2012:247597. https://doi.org/10.1155/2012/247597

    Article  CAS  PubMed  Google Scholar 

  102. Chaturvedi D, Goswami A, Saikia PP, Barua NC, Rao PG et al (2010) Artemisinin and its derivatives: a novel class of anti-malarial and anti-cancer agents. Chem Soc Rev 39(2):435–454

    CAS  PubMed  Google Scholar 

  103. Efferth T (2006) Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets 7:407–421

    CAS  PubMed  Google Scholar 

  104. Reichert S, Reinboldt V, Hehlgans S, Efferth T, Rodel C, Rodel F et al (2012) A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein survivin. Radiother Oncol 103:394–401. https://doi.org/10.1016/j.radonc.2012.03.018

    Article  CAS  PubMed  Google Scholar 

  105. Michaelis M (2010) Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines. Biochem Pharmacol 79(2):130–136

    CAS  PubMed  Google Scholar 

  106. Efferth T, Merling A, Krammer PH, Li-Weber M et al (2007) Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS ONE 2(8):693

    Google Scholar 

  107. Hamacher-Brady A, Stein HA, Turschner S, Toegel I, Mora R, Jennewein N, Efferth T, Eils R, Brady NR et al (2011) Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. J Biol Chem 286(8):6587–6601

    CAS  PubMed  Google Scholar 

  108. Zeng QP, Zhang PZ (2011) Artesunate mitigates proliferation of tumor cells by alkylating heme-harboring nitric oxide synthase. Nitric Oxide 24(2):110–112

    CAS  PubMed  Google Scholar 

  109. Du JH, Zhang HD, Ma ZJ, Ji KM et al (2010) Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo. Cancer Chemother Pharmacol 65(5):895–902

    CAS  PubMed  Google Scholar 

  110. Anfosso L, Efferth T, Albini A, Pfeffer U et al (2006) Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenom J 6:269–278

    CAS  Google Scholar 

  111. Lai HC, Singh NP, Sasaki T et al (2013) Development of artemisinin compounds for cancer treatment. Invest New Drugs 31(1):230–246

    CAS  PubMed  Google Scholar 

  112. Li LN, Zhang HD, Yuan SJ, Tian ZY, Wang L, Sun ZX et al (2007) Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/β-catenin pathway. Int J Cancer 121(6):1360–1365

    CAS  PubMed  Google Scholar 

  113. Eling N, Reuter L, Hazin J, Hamacher-Brady A, Brady NR et al (2015) Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience 2(5):517–532

    PubMed  PubMed Central  Google Scholar 

  114. Chen HH, Zhou HJ, Fang X et al (2003) Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro. Pharmacol Res 48(3):231–236

    CAS  PubMed  Google Scholar 

  115. Zhou HJ, Wang WQ, Wu GD, Lee J, Li A et al (2007) Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells. Vascul Pharmacol 47(2):131–138

    CAS  PubMed  Google Scholar 

  116. Youns M, Efferth T, Reichling J, Fellenberg K, Bauer A, Hoheisel JD et al (2009) Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells. Biochem Pharmacol 78:273–283

    CAS  PubMed  Google Scholar 

  117. Rasheed SAK, Efferth T, Asangani IA, Allgayer H et al (2010) First evidence that the antimalarial drug artesunate inhibits invasion and in vivo metastasis in lung cancer by targeting essential extracellular proteases. Int J Cancer 127:1475–1485

    CAS  PubMed  Google Scholar 

  118. Li LN, Zhang HD, Yuan SJ, Yang DX, Wang L, Sun ZX et al (2008) Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin. Eur J Pharmacol 588(1):1–8

    CAS  PubMed  Google Scholar 

  119. Lai H, Nakase I, Lacoste E, Singh NP, Sasaki T et al (2009) Artemisinin-transferrin conjugate retards growth of breast tumors in the rat. Anticancer Res 29(10):3807–3810

    CAS  PubMed  Google Scholar 

  120. Nakase I, Gallis B, Takatani-Nakase T, Oh S, Lacoste E, Singh NP, Goodlett DR, Tanaka S, Futaki S, Lai H, Sasaki T et al (2009) Transferrin receptor-dependent cytotoxicity of artemisinin–transferrin conjugates on prostate cancer cells and induction of apoptosis. Cancer Lett 274(2):290–298

    CAS  PubMed  Google Scholar 

  121. Nakase I, Lai H, Singh NP, Sasaki T et al (2008) Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm 354:28–33

    CAS  PubMed  Google Scholar 

  122. Singh NP, Verma K (2002) Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 10(4):279–280

    Google Scholar 

  123. Berger TG, Dieckmann D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G et al (2005) Artesunate in the treatment of metastatic uveal melanoma-first experiences. Oncol Rep 14:1599–1604

    CAS  PubMed  Google Scholar 

  124. Zhang Z, Yu SQ, Miao LY, Huang XY, Zhang XP, Zhu YP, Xia XH, Li DQ et al (2008) Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao = J Chin Integr Med 6(2):134–138

    CAS  Google Scholar 

  125. Lu JJ, Meng LH, Shankavaram UT, Zhu CH, Tong LJ, Chen G, Lin LP, Weinstein JN, Ding J et al (2010) Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells. Biochem Pharmacol 80(1):22–30

    CAS  PubMed  Google Scholar 

  126. Lu YY, Chen TS, Qu JL, Pan WL, Sun L, Wei XB et al (2009) Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. J Biomed Sci 16:16–20

    PubMed  PubMed Central  Google Scholar 

  127. Lu YY, Chen TS, Wang XP, Qu JL, Chen M et al (2010) The JNK inhibitor SP600125 enhances dihydroartemisinin-induced apoptosis by accelerating Bax translocation into mitochondria in human lung adenocarcinoma cells. FEBS Lett 584:4019–4026

    CAS  PubMed  Google Scholar 

  128. Riganti C, Doublier S, Viarisio D, Miraglia E, Pescarmona G, Ghigo D et al (2009) Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1αand P-glycoprotein overexpression. Br J Pharmacol 156:1054–1066

    CAS  PubMed  PubMed Central  Google Scholar 

  129. D’Alessandro S, Basilico N, Corbett Y, Scaccabarozzi D, Omodeo-Sale F, Saresella M, Marventano I, Vaillant M, Olliaro P, Taramelli D et al (2011) Hypoxia modulates the effect of dihydroartemisinin on endothelial cells. Biochem Pharmacol 82:476–484

    PubMed  Google Scholar 

  130. Zhang J, Li L, Liu X, Wang Y, Zhao D et al (2012) Study on chemical constituents of Artemisia sphaerocephala. China J Chin Materia Med 37(2):238–242

    Google Scholar 

  131. Zhang CZ, Zhang H, Yun J, Chen GG, Lai PB et al (2012) Dihydroartemisinin exhibits antitumor activity toward hepatocellular carcinoma in vitro and in vivo. Biochem Pharmacol 83(9):1278–1289

    CAS  PubMed  Google Scholar 

  132. Wang SJ (2010) Dihydroartemisinin inactivates NF-??B and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo. Cancer Lett 293(1):99–108

    CAS  PubMed  Google Scholar 

  133. Wang SJ (2011) Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-??B pathway. Cancer Chemother Pharmacol 68(6):1421–1430

    CAS  PubMed  Google Scholar 

  134. Wu XL, Zhang WG, Shi XM, An P, Sun WS, Qiao CL, Wang Z et al (2011) Effect of artemisinin on the expressions of GRalpha mRNA, GRbeta mRNA and P300/CBP protein in lupus nephritis mice. J Chin Med Mater 17(4):277–282

    CAS  Google Scholar 

  135. Wang J, Zhang C-J, Chia WN et al (2015) Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nat Commun 6:10111

    CAS  PubMed  Google Scholar 

  136. D’Alessandro S, Gelati M, Basilico N, Parati EA, Haynes RK, Taramelli D et al (2007) Differential effects on angiogenesis of two antimalarial compounds, dihydroartemisinin and artemisone: implications for embryotoxicity. Toxicology 241(1):66–74

    PubMed  Google Scholar 

  137. Wei-Ling X, Pei-Hui Y, Zeng X, Ji-Ye C et al (2009) Effect of 4-(12-dihydroartemisininoxy) benzoic acid hydrazide transferrin tagged drug on human breast cancer cells. Chin J Anal Chem 37(5):671–675

    Google Scholar 

  138. Singh NP, Panwar VK (2006) Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther 5:391–394

    PubMed  Google Scholar 

  139. Farsam V, Hassan ZM, Zavaran-Hosseini A, Noori S, Mahdavi M, Ranjbar M et al (2011) Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo. Int Immunopharmacol 11:1802–1808

    CAS  PubMed  Google Scholar 

  140. Alcântara DDFÁ, Ribeiro HF, Cardoso PCS, Araújo TMT, Burbano RR, Guimarães AC, Khayat AS, Oliveira BM et al (2013) In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100). J Appl Toxicol 33:151–156

    PubMed  Google Scholar 

  141. Zhao Y, Jiang W, Li B, Yao Q, Dong J, Chen Y, Pan X, Li J, Zheng J, Pang X et al (2011) Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing no production to induce cell cycle arrest at G 2/M phase. Int Immunopharmacol 11:2039–2046

    CAS  PubMed  Google Scholar 

  142. Efferth T, Oesch F (2004) Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines. Biochem Pharmacol 68:3–10

    CAS  PubMed  Google Scholar 

  143. Luthria DL (2006) Significance of sample preparation in developing analytical methodologies for accurate estimation of bioactive compounds in functional foods. J Sci Food Agric 86(14):2266–2272

    CAS  Google Scholar 

  144. Castellano G, Tena J, Torrens F et al (2012) Classification of phenolic compounds by chemical structural indicators and its relation to antioxidant properties of posidonia oceanica (L.) Delile. Environment 2:6–9

    Google Scholar 

  145. Ferreira JF, Luthria DL, Sasaki T, Heyerick A et al (2010) Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules 15(5):3135–3170

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Croteau R, Kutchan T, Lewis N et al (2000) Natural products (secondary metabolites). Biochem Mol Biol Plants 24:1250–1319

    Google Scholar 

  147. Debeaujon I, Peeters AJ, Léon-Kloosterziel KM, Koornneef M et al (2001) The TRANSPARENT TESTA12 gene of Arabidopsis encodes a multidrug secondary transporter-like protein required for flavonoid sequestration in vacuoles of the seed coat endothelium. Plant Cell 13(4):853–871

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Kitamura S (2006) Transport of flavonoids: from cytosolic synthesis to vacuolar accumulation. The science of flavonoids. Springer, Cham, pp 123–146

    Google Scholar 

  149. Grassi D, Desideri G, Ferri C et al (2010) Flavonoids: antioxidants against atherosclerosis. Nutrients 2:889–902

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Middleton JR (1998) Effect of plant flavonoids on immune and inflammatory cell function. Flavonoids in the living system. Springer, Cham, pp 175–182

    Google Scholar 

  151. Falcone Ferreyra ML, Rius S, Casati P et al (2012) Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front Plant Sci 3:222

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Aberham A, Cicek SS, Schneider P, Stuppner H et al (2010) Analysis of sesquiterpene lactones, lignans, and flavonoids in wormwood (Artemisia absinthium L.) using high-performance liquid chromatography (HPLC)—mass spectrometry, reversed phase HPLC, and HPLC—solid phase extraction—nuclear magnetic resonance. J Agric Food Chem 58(20):10817–10823

    CAS  PubMed  Google Scholar 

  153. Singh R, Verma PK, Singh G et al (2012) Total phenolic, flavonoids and tannin contents in different extracts of Artemisia absinthium. J Intercult Ethnopharmacol 1(2):101–104

    Google Scholar 

  154. Hajdú Z, Martins A, Orbán-Gyapai O, Forgo P, Jedlinszki N, Máthé I, Hohmann J et al (2014) Xanthine oxidase-inhibitory activity and antioxidant properties of the methanol extract and flavonoids of Artemisia asiatica. Rec Nat Prod 8(3):299

    Google Scholar 

  155. Qnais E, Raad D, Bseiso Y et al (2014) Analgesic and anti-inflammatory effects of an extract and flavonoids from Artemisia herba-alba and their mechanisms of action. Neurophysiology 46(3):238–246

    CAS  Google Scholar 

  156. Suresh J, Ahuja J, Paramakrishnan N, Sebastian M et al (2012) Total phenolic and total flavonoids content of aerial parts of Artemisia abrotanum Linn. and A. pallens wall. Anal Chem Lett 2(3):186–191

    CAS  Google Scholar 

  157. Xiao M, Luo D, Ke Z, Ye J, Tu PF (2014) A novel polyacetylene from the aerial parts of Artemisia lactiflora. Phytochem Lett 8:52–54

    CAS  Google Scholar 

  158. Mabeza GF, Loyevsky M, Gordeuk VR, Weiss G et al (1999) Iron chelation therapy for malaria: a review. Pharmacol Ther 81(1):53–75

    CAS  PubMed  Google Scholar 

  159. Lai H, Singh NP (1995) Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett 91(1):41–46

    CAS  PubMed  Google Scholar 

  160. Moore JC, Lai H, Li JR, Ren RL, McDougall JA, Singh NP, Chou CK et al (1995) Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Lett 98(1):83–87

    CAS  PubMed  Google Scholar 

  161. Li XY, Zhao Y, Sun MG, Shi JF, Ju RJ, Zhang CX, Lu WL et al (2014) Multifunctional liposomes loaded with paclitaxel and artemether for treatment of invasive brain glioma. Biomaterials 35(21):5591–5604. https://doi.org/10.1016/j.biomaterials.2014.03.049

    Article  CAS  PubMed  Google Scholar 

  162. Li P, Yang S, Dou M, Chen Y, Zhang J, Zhao X et al (2014) Synergic effects of artemisinin and resveratrol in cancer cells. J Cancer Res Clin Oncol 140(12):2065–2075

    CAS  PubMed  Google Scholar 

  163. Dilshad E, Zafar S, Ismail H, Waheed MT, Cusido RM, Palazon J, Mirza B (2016) Effect of rol genes on polyphenols biosynthesis in Artemisia annua and their effect on antioxidant and cytotoxic potential of the plant. Appl Biochem Biotechnol 179(8):1456–1468

    CAS  PubMed  Google Scholar 

  164. Dilshad E, Ismail H, Khan MA, Cusido RM, Mirza B (2020) Metabolite profiling of Artemisia carvifolia Buch transgenic plants and estimation of their anticancer and antidiabetic potential. Biocatal Agric Biotechnol 24:101539

    Google Scholar 

  165. Tolomeo M, Grimaudo S, Di Cristina A, Roberti M, Pizzirani D, Meli M, Dusonchet L, Gebbia N, Abbadessa V, Crosta L et al (2005) Pterostilbene and 3′-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells. Int J Biochem Cell Biol 37(8):1709–1726

    CAS  PubMed  Google Scholar 

  166. Yeon J, Raj C, Thapa K, Soon C, Jong Y, Kim O et al (2016) Nanoparticle-based combination drug delivery systems for synergistic cancer treatment. J Pharm Investig. https://doi.org/10.1007/s40005-016-0252-1

    Article  Google Scholar 

  167. Ochiuz L, Grigoras C, Popa M, Stoleriu I, Munteanu C, Timofte D, Grigoras AG et al (2016) Alendronate-loaded modified drug delivery lipid particles intended for improved oral and topical administration. Molecules 21(7):858. https://doi.org/10.3390/molecules21070858

    Article  CAS  PubMed Central  Google Scholar 

  168. Gharib A, Faezizadeh Z, Mesbah-Namin SA, Saravani R et al (2014) Preparation, characterization and in vitro efficacy of magnetic nanoliposomes containing the artemisinin and transferrin. Daru 22(1):44–50. https://doi.org/10.1186/2008-2231-22-44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Wu GS (2013) Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells. Pharmacol Rep 65(2):453–459

    CAS  PubMed  Google Scholar 

  170. Eltayeb SE, Su Z, Xiao Y, Ping Q et al (2016) Antitumor activity of transferrin-modified- artemether lipid nanospheres in cancer cell lines. J Drug Deliv Sci Technol 31:118–129. https://doi.org/10.1016/j.jddst.2015.12.003

    Article  CAS  Google Scholar 

  171. Nguyen DX, Massague J (2014) Genetic determinants of cancer metastasis. Nat Rev Genet 8:341–352

    Google Scholar 

  172. Jiang W, Huang Y, Wang J, Yu X, Zhang L et al (2013) The synergistic anticancer effect of artesunate combined with allicin in osteosarcoma cell line in vitro and in vivo. Asian Pac J Cancer Prev 14:4615–4619

    PubMed  Google Scholar 

  173. Krusche B, Arend J, Efferth T et al (2013) Synergistic inhibition of angiogenesis by artesunate and captopril in vitro and in vivo. Evid Based Complement Altern Med. https://doi.org/10.1155/2013/454783

    Article  Google Scholar 

Download references

Acknowledgements

Dr. John Suberu, Department of Chemical Engineering and Biotechnology, University of Cambridge, is acknowledged for the proof reading of the paper.

Funding

Funding information is not applicable/No funding was received.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Faculty of Basic and Applied Sciences, International Islamic University, Islamabad, 44000, Pakistan

    Bushra Hafeez Kiani

  2. Department of Plant Breeding, Swedish University of Agricultural Sciences, Växtskyddsvägen 1, 23053, Alnarp, Sweden

    Waqas Khan Kayani

  3. Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Asma Umer Khayam & Bushra Mirza

  4. Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad, Pakistan

    Erum Dilshad

  5. Department of Biochemistry and Molecular Biology, University of Gujrat, Gujrat, 50700, Pakistan

    Hammad Ismail

Authors
  1. Bushra Hafeez Kiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Waqas Khan Kayani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Asma Umer Khayam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erum Dilshad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hammad Ismail
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bushra Mirza
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BHK conceived and designed the study. BHK, WKK, AUK, HI and ED wrote the manuscript. BM reviewed the manuscript. All the authors read and approved the manuscript.

Corresponding author

Correspondence to Bushra Hafeez Kiani.

Ethics declarations

Conflict of interest

The authors declare that they do not have any competing interests.

Ethical approval

No ethical considerations apply for this review paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kiani, B.H., Kayani, W.K., Khayam, A.U. et al. Artemisinin and its derivatives: a promising cancer therapy. Mol Biol Rep 47, 6321–6336 (2020). https://doi.org/10.1007/s11033-020-05669-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05669-z

Keywords

Search

Navigation