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Anticancer Terpenoids

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New Approaches to Natural Anticancer Drugs

Part of the book series: SpringerBriefs in Pharmaceutical Science & Drug Development ((BRIEFSPSDD))

Abstract

Terpenoids are a class of secondary metabolites with immense variety of structures and biological activity. They are divided into some groups including monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids and tetraterpenoids. Among them, there are some compounds with interesting anticancer activity capable for use in clinical or pre-clinical administration like D-limonene, perilyll alcohol and salvicine, as well as drugs derived from parthenolide, thapsigargin and artemisinin. Off-target effects, low bioavailability and adverse effects of some terpenoids like parthenolide derivatives make them unsuitable for clinical application. However, they can play a role as lead compounds for the development of semi-synthetic molecules, in which specificity and pharmacokinetic parameters would be improved. In addition, some of these compounds such as salvicine, triterpenoids and carotenoids have been able to overcome multi drug resistance by inhibition of p-glycoprotein overexpression in cancer cells demonstrating them as the proper candidate for co-administration with chemotherapy agents. Moreover, combination of these compounds with anticancer drugs may enhance the efficacy and decrease adverse effects of both drug and terpenoids.

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References

  • Bishayee A, Ahmed Sh, Brankov N, Perloff M (2011) Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci 16:980–996.

    Google Scholar 

  • Bolhassani A, Khavari A, Bathaie SZ (2014) Saffron and natural carotenoids: biochemical activities and anti-tumor effects. Biochim Biophys Acta 1845:20–30

    CAS  PubMed  Google Scholar 

  • Cai YJ, Lu JJ, Zhu H, Xie H, Huang M, Lin LP, Zhang XW, Ding J (2008) Salvicine triggers DNA double-strand breaks and apoptosis by GSH-depletion-driven H2O2 generation and topoisomerase II inhibition. Free Radic Biol Med 45:627–635

    Article  CAS  PubMed  Google Scholar 

  • Cavin C, Holzhaeuser D, Scharf G, Constable A, Huber WW, Schilter B (2002) Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem Toxicol 40:1155–1163

    Article  CAS  PubMed  Google Scholar 

  • Chadwick M, Trewin H, Gawthrop F, Wagstaff C (2013) Sesquiterpenoids lactones: benefits to plants and people. Int J Mol Sci 14:12780–12805

    Article  PubMed Central  PubMed  Google Scholar 

  • Chang H, Chyau CC, Hsieh CL, Wu Y, Ker YB, Tsen HY, Peng RY (2008) Relevance of phenolic diterpene constituents to antioxidant activity of supercritical CO(2) extract from the leaves of rosemary. Nat Prod Res 22:76–90

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi D (2011) Sesquiterpene lactones: structural diversity and their biological activities in opportunity, challenge and scope of natural products in medicinal chemistry. Signpost, Kerala

    Google Scholar 

  • Chen JC, Chiu MH, Nie RL, Cordell GA, Qiu SX (2005) Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep 22:386–399

    Article  CAS  PubMed  Google Scholar 

  • Cheng D, Xiao J, Cheng H, Liu Z, Covey JM, Chan K (2005) Analytical method development and pharmacokinetics studies with parthenolide (NSC 157035) and a water-soluble analog (NSC 734325). AACR Meeting Abstracts 1:988

    Google Scholar 

  • Fonrose X, Ausseil F, Soleilhac E, Masson V, David B, Pouny I, Cintrat JC, Rousseau B, Barette C, Massiot G, Lafanechère L (2007) Parthenolide inhibits tubulin carboxypeptidase activity. Cancer Res 67:3371–3378

    Article  CAS  PubMed  Google Scholar 

  • Fonseca C, Landeiro JA, Clark S, Quirico-Santos S, Carvalho T, Gattass CR (2006) Recent advances in the molecular genetics of malignant gliomas disclose targets for antitumor agent perillyl alcohol. Surg Neurol 65:S1:2–S1:9

    Article  Google Scholar 

  • Fonseca C, Schwartsmann G, Fischer J, Nagel J, Futuro D, Quirico-Santos T, Gattass CR (2008) Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas. Surg Neurol 70:259–267

    Article  PubMed  Google Scholar 

  • Fulda S, Debatin KM (2000) Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. Med Pediatr Oncol 35:616–618

    Article  CAS  PubMed  Google Scholar 

  • Fulda S, Kroemer G (2009) Targeting mitochondrial apoptosis by betulinic acid in human cancers. Drug Discov Today 14:885–890

    Article  CAS  PubMed  Google Scholar 

  • Gana HK, Kaye AH, Luwor RB (2009) The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci 16:748–754

    Article  Google Scholar 

  • Garattini E, Gianni M, Terao M (2007) Retinoids as differentiating agents in oncology: a network of interactions with intracellular pathways basis for rational therapeutic combinations. Curr Pharm Des 13:1375–1400

    Article  CAS  PubMed  Google Scholar 

  • Ghantous A, Ghantous H, Vuorela H, Saliba A, Darwiche N (2010) What made sesquiterpene lactones reach cancer clinical trials? Drug Discov Today 15:668–678

    Article  CAS  PubMed  Google Scholar 

  • Ghantous A, Sinjab A, Herceg Z, Darwiche N (2013) Parthenolide: from plant shoots to cancer roots. Drug Discov Today 18:894–905

    Article  CAS  PubMed  Google Scholar 

  • Gunn EJ, Williams JT, Huynh DT, Iannotti MJ, Han C, Barrios FJ, Kendall S, Glackin CA, Colby DA, Kirshner J (2011) The natural products parthenolide and andrographolide exhibit anticancer stem cell activity in multiple myeloma. Leuk Lymphoma 52:1085–1097

    Article  CAS  PubMed  Google Scholar 

  • Guo Z, Vangapandu S, Sindelar RW, Walker LA, Sindelar RD (2005) Biologically active quassinoids and their chemistry: potential leads for drug design. Curr Med Chem 12:173–190

    Article  CAS  PubMed  Google Scholar 

  • Guzman ML, Jordan CT (2005) Feverfew: weeding out the root of leukemia. Expert Opin Biol Ther 5:1147–1152

    Article  CAS  PubMed  Google Scholar 

  • Harries M, O’Donnell A, Scurr M, Reade S, Cole C, Judson I, Greystoke A, Twelves C, Kaye S (2004) Phase I/II study of DHA-paclitaxel in combination with carboplatin in patients with advanced malignant solid tumours. Br J Cancer 91:1651–1655

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hu CX, Zuo ZL, Xiong B, Ma JG, Geng MY, Lin LP, Jiang HL, Ding J (2006) Salvicine functions as novel topoisomerase II poison by binding to ATP pocket. Mol Pharmacol 70: 1593–1601.

    Google Scholar 

  • Huang M, Lu JJ, Huang MQ, Bao JL, Chen XP, Wang YT (2012) Terpenoids: natural products for cancer therapy. Expert Opin Invest Drugs 21(12):1801–1818

    Article  CAS  Google Scholar 

  • Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, Rivera E, Esmaeli B, Ring SE, Bedikian A, Hortobagyi GN, Ellerhorst JA (2002) Phase I and pharmacokinetic study of ABI007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 8:1038–1044

    CAS  PubMed  Google Scholar 

  • Johnson JJ (2011) Carnosol: a promising anticancer and anti-inflammatory agent. Cancer Lett 305:1–7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Johnson JJ, Syed DN, Suh Y, Heren CR, Saleem M, Siddiqui IA, Mukhtar H (2010) Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention. Cancer Prev Res 3:1112–1123

    Article  CAS  Google Scholar 

  • Jung MJ, Yoo YC, Lee KB, Kim JB, Song KS (2004) Isolation of epi-oleanolic acid from Korean mistletoe and its apoptosis-inducing activity in tumor cells. Arch Pharm Res 27:840–844

    Article  CAS  PubMed  Google Scholar 

  • Khan N, Afaq F, Mukhtar H (2007) Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis 28:233–239

    Article  CAS  PubMed  Google Scholar 

  • Kuzuyama T (2002) Mevalonate and nonmevalonate pathways for biosynthesis of isoprene units. Biosci Biotechnol Biochem 66:1619–1627

    Article  CAS  PubMed  Google Scholar 

  • Kuzuyama T, Seto H (2012) Two distinct pathways for essential metabolic precursors for isoprenoid biosynthesis. Proc Jpn Acad Ser B Phys Biol Sci 88:41–52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lang JY, Chen H, Zhou J, Zhang YX, Zhang XW, Li MH, Lin LP, Zhang JS, Waalkes MP, Ding J (2005) Antimetastatic effect of salvicine on human breast cancer MDAMB-435 orthotopic xenograft is closely related to Rho-dependent pathway. Clin Cancer Res 11:3455–3464

    Article  CAS  PubMed  Google Scholar 

  • Laszczyk MN (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med 75:1549–1560

    Article  CAS  PubMed  Google Scholar 

  • Lee DH, Iwanski GB, Thoennisson NH (2010) Cucurbitacin: ancient compound shedding new light on cancer treatment. Sci World J 10:413–418

    Article  CAS  Google Scholar 

  • Liu Z (2009) Modulation of DNA methylation by a sesquiterpene lactone parthenolide. J Pharmacol Exp Ther 329:505–514

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu WJ, Jiang JF, Xiao D, Ding J (2002) Down-regulation of telomerase activity via protein phosphatase 2A activation in salvicine-induced human leukemia HL-60 cell apoptosis. Biochem Pharmacol 64:1677–1687

    Article  CAS  PubMed  Google Scholar 

  • Liu WJ, Zhang YW, Shen Y, Jiang JF, Miao ZH, Ding J (2004) Telomerase inhibition is a specific early event in salvicine-treated human lung adenocarcinoma A549 cells. Biochem Biophys Res Commun 323:660–667

    Article  CAS  PubMed  Google Scholar 

  • Lu HR, Zhu H, Huang M, Chen Y, Cai YJ, Miao ZH, Zhang JS, Ding J (2005) Reactive oxygen species elicit apoptosis by concurrently disrupting topoisomerase II and DNA-dependent protein kinase. Mol Pharmacol 68:983–994

    Article  CAS  PubMed  Google Scholar 

  • Lu F, Liu HY, Lin LP, Ding J, Zhang JS (2011) Synthesis and antitumor activity of novel salvicine analogue. Chin Chem Lett 22:25–28

    Article  Google Scholar 

  • Martin R, Carvalho J, Ibeas E, Hernandez M, Ruiz-Gutierrez V, Nieto ML (2007) Acidic triterpenes compromise growth and survival of astrocytoma cell lines by regulating reactive oxygen species accumulation. Cancer Res 67:3741–3751

    Article  CAS  PubMed  Google Scholar 

  • Meng LH, Ding J (2007) Salvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation. Acta Pharmacol Sin 28(9):1460–1465

    Article  CAS  PubMed  Google Scholar 

  • Miao ZH, Tang T, Zhang YX, Zhang JS, Ding J (2003) Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells. Int J Cancer 106:108–115

    Article  CAS  PubMed  Google Scholar 

  • Molina JR, Adjei AA (2006) The Ras/Raf/MAPK pathway. J Thorac Oncol 1:7–9

    Article  PubMed  Google Scholar 

  • Murtaza I, Saleem M, Adhami VM, Hafeez BB, Hafeez H (2009) Suppression of cFLIP by lupeol, a dietary triterpene, is sufficient to overcome resistance to TRAIL-mediated apoptosis in chemoresistant human pancreatic cancer cells. Cancer Res 69:1156–1165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nasim S, Crooks PA (2008) Antileukemic activity of aminoparthenolide analogs. Bioorg Med Chem Lett 18:3870–3873

    Article  CAS  PubMed  Google Scholar 

  • Neelakantan S, Nasim S, Guzman ML, Jordan CT, Crooks PA (2009) Amino parthenolides as novel anti-leukemic agents: discovery of the NF-kappaB inhibitor, DMAPT (LC-1). Bioorg Med Chem Lett 19:4346–4349

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66:1022–1037

    Article  CAS  PubMed  Google Scholar 

  • Osaki M, Oshimura M, Ito H (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9:667–676

    Article  CAS  PubMed  Google Scholar 

  • Palozza P, Serini S, Di-Nicuolo F, Calviello G (2004) Modulation of apoptotic signaling by carotenoids in cancer cells. Arch Biochem Biophys 430:104–109

    Article  CAS  PubMed  Google Scholar 

  • Pandey MK, Sung B, Aggarwal BB (2010) Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP1 in human multiple myeloma cells. Int J Cancer 127:282–292

    PubMed Central  CAS  PubMed  Google Scholar 

  • Peese K (2010) New agents for the treatment of leukemia: discovery of DMAPT (LC1). Drug Discov Today 15:253–324

    Article  Google Scholar 

  • Prasad S, Madan E, Nigam N, Roy P, George J, Shukla Y (2009) Induction of apoptosis by lupeol in human epidermoid carcinoma A431 cells through regulation of mitochondrial, Akt/PKB and NFkappaB signaling pathways. Cancer Biol Ther 8:1632–1639

    Article  CAS  PubMed  Google Scholar 

  • Saleem M, Afaq A, Adhami VM, Mukhtar H (2004) Lupeol modulates NFkappa B and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice. Oncogene 23:5203–5214

    Article  CAS  PubMed  Google Scholar 

  • Shanmugam M, Nguyen A, Kumar AP, Tan B, Sethi G (2012) Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer. Cancer Lett 320:158–170

    Article  CAS  PubMed  Google Scholar 

  • Shishodia S, Majumdar S, Banerjee S, Aggarwal BB (2003) Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res 63:4375–4383

    CAS  PubMed  Google Scholar 

  • Siddique HR, Saleem M (2011) Beneficial health effects of lupeol triterpene: a review of preclinical studies. Life Sci 88:285–293

    Article  CAS  PubMed  Google Scholar 

  • Spigel DR, Greco FA (2008) What is the role of novel taxanes in non-small-cell lung cancer? Clin Lung Cancer 9:S116–S121

    Article  PubMed  Google Scholar 

  • Sultana S, Saleem M, Sharma S, Khan N (2003) Lupeol, a triterpene, prevents free radical mediated macromolecular damage and alleviates benzoyl peroxide induced biochemical alterations in murine skin. Indian J Exp Biol 41:827–831

    CAS  PubMed  Google Scholar 

  • Sun J (2007) D-limonene: safety and clinical application. Altern Med Rev 12:259–264

    PubMed  Google Scholar 

  • Tada M, Ohkanda T, Kurabe J (2010) Syntheses of carnosic acid and carnosol, anti-oxidants in Rosemary, from pisiferic acid, the major constituent of Sawara. Chem Pharm Bull 58:27–29

    Article  CAS  PubMed  Google Scholar 

  • Valent P, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, Chomienne C, Ishikawa F, Schuringa JJ, Stassi G, Huntly B, Herrmann H, Soulier J, Roesch A, Schuurhuis GJ, Wöhrer S, Arock M, Zuber J, Cerny-Reiterer S, Johnsen HE, Andreeff M, Eaves C (2012) Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer 12:767–775

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Mao Y, Chen AY, Zhou N, LaVoie EJ, Liu LF (2001) Stimulation of topoisomerase II-mediated DNA damage via a mechanism involving protein thiolation. Biochemistry 40:3316–3323

    Article  CAS  PubMed  Google Scholar 

  • Yehia Eid S, El-Readi MZ, Wink M (2012) Carotenoids reverse multidrug resistance in cancer cells by interfering with ABC- transporters. Phytomedicine 19:977–987

    Article  Google Scholar 

  • Zhang P, Li H, Chen D, Ni J, Kang Y, Wang S (2007) Oleanolic acid induces apoptosis in human leukemia cells through caspase activation and poly(ADPribose) polymerase cleavage. Acta Biochim Biophys Sin (Shanghai) 39:803–809

    Article  CAS  Google Scholar 

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  1. Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Soodabeh Saeidnia

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Saeidnia, S. (2015). Anticancer Terpenoids. In: New Approaches to Natural Anticancer Drugs. SpringerBriefs in Pharmaceutical Science & Drug Development. Springer, Cham. https://doi.org/10.1007/978-3-319-14027-8_5

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  • DOI: https://doi.org/10.1007/978-3-319-14027-8_5

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  • Publisher Name: Springer, Cham

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