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Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer

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Abstract

Natural products have become increasingly important in pharmaceutical discoveries, and traditional herbalism has been a pioneering specialty in biomedical science. The search for effective plant-derived anticancer agents has continued to gain momentum in recent years. The present study aimed to investigate the role of crude extracts of the aerial parts of Artemisia absinthium (AA) extract in modulating intracellular signaling mechanisms, in particular its ability to inhibit cell proliferation and promote apoptosis in a human breast carcinoma estrogenic-unresponsive cell line, MDA-MB-231, and an estrogenic-responsive cell line, MCF-7. Cells were incubated with various concentrations of AA, and anti-proliferative activity was assessed by MTT assays, fluorescence microscopy after propidium iodide staining, western blotting and cell cycle analysis. Cell survival assays indicated that AA was cytotoxic to both MDA-MB-231 and MCF-7 cells. The morphological features typical of nucleic staining and the accumulation of sub-G1 peak revealed that the extract triggered apoptosis. Treatment with 25 μg/mL AA resulted in activation of caspase-7 and upregulation of Bad in MCF-7 cells, while exposure to 20 μg/mL AA induced upregulation of Bcl-2 protein in a time-dependent response in MDA-MB-231 cells. Both MEK1/2 and ERK1/2 was inactivated in both cell lines after AA treatment in a time-dependent manner. These results suggest that AA-induced anti-proliferative effects on human breast cancer cells could possibly trigger apoptosis in both cell lines through the modulation of Bcl-2 family proteins and the MEK/ERK pathway. This might lead to its possible development as a therapeutic agent for breast cancer following further investigations.

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References

  1. Koul MK (1997) Medicinal Plants of Kashmir and Ladakh, Temperate and Cold Arid Himalaya, Indus Publishing Company, FS-5, Tagore Garden, New Delhi p 102, ISBN: 81-7837-061-6

  2. Juteau F, Jerkovic I, Masotti V, Milos M, Mastelic J, Bessiere JM, Viano J (2003) Composition and anti-microbial activity of essential oil of Artemisia absinthium from Croatia and France. Planta Med 69:158–161

    Article  PubMed  CAS  Google Scholar 

  3. Saban K, Recep M, Ahmet CAA, Ali Y (2005) Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, Artemisia dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. J Agric Food Chem 53:9452–9458

    Article  Google Scholar 

  4. Meschler JP, Howlett AC (1999) Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses. Pharm Biochem Behav 62:413–480

    Article  Google Scholar 

  5. Baytop (1984) Therapy with Medicinal Plants in Turkey. Istanbul University Press, Istanbul, pp 166–167

    Google Scholar 

  6. Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW et al (2005) Chemopreventive properties of the ethanol extract of Chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett 230:239–247

    Article  PubMed  CAS  Google Scholar 

  7. Wu CC, Chan ML, Chen WY, Tsai CY, Chang FR, Wu YC (2005) Pristimerin induces caspase-dependent apoptosis in MDA-MB-231 cells via direct effects on mitochondria. Mol Cancer Ther 4:1277–1285

    Article  PubMed  CAS  Google Scholar 

  8. Garcia-Carbonero R, Supko JG (2002) Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res 8:641–661

    PubMed  CAS  Google Scholar 

  9. Rowinsky EK, Donehower RC (1995) Paclitaxel (taxol). N Engl J Med 332:1004–1014

    Article  PubMed  CAS  Google Scholar 

  10. Zhu JY, Lavrik IN, Mahlknecht U, Giaisi M, Proksch P, Krammer PH, Li- Weber M (2007) The traditional Chinese herbal compound rocaglamide preferentially induces apoptosis in leukemia cells by modulation of mitogen-activated protein kinase activities. Int J Cancer 121:1839–1846

    Article  PubMed  CAS  Google Scholar 

  11. Huang M, Gao H, Chen Y, Zhu H, Cai Y, Zhang X, Miao Z, Jiang H, Zhang J, Shen H, Lin L, Lu W, Ding J (2007) Chimmitecan, a novel 9-substituted camptothecin, with improved anticancer pharmacologic profiles in vitro and in vivo. Clin Cancer Res 13:1298–1307

    Article  PubMed  CAS  Google Scholar 

  12. Tamvakopoulos C, Dimas K, Sofianos ZD, Hatziantoniou S, Han Z, Liu ZL, Wyche JH, Pantazis P (2007) Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin. Clin Cancer Res 13:1269–1277

    Article  PubMed  CAS  Google Scholar 

  13. Li L, Gao Y, Zhang L, Zeng J, He D, Sun Y (2008) Silibinin inhibits cell growth and induces apoptosis by caspase activation, downregulating surviving and blocking EGFR-ERK activation in renal cell carcinoma. Cancer Lett 272:61–69

    Article  PubMed  CAS  Google Scholar 

  14. Razis ED, Fountzilas G (2001) Paclitaxel: epirubicin in metastatic breast cancer–a review. Ann Oncol 12:593–598

    Article  PubMed  CAS  Google Scholar 

  15. Hainsworth JD, Greco FA (1995) Etoposide: twenty years later. Ann Oncol 6:325–341

    PubMed  CAS  Google Scholar 

  16. Jordan MA, Thrower D, Wilson L (1991) Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 51:2212–2222

    PubMed  CAS  Google Scholar 

  17. Ganry O (2002) Phytoestrogen and breast cancer prevention. Eur J Cancer Prev 11:519–522

    Article  PubMed  CAS  Google Scholar 

  18. Sun SY, Hail N, Lotan R (2004) Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 96:662–672

    Article  PubMed  CAS  Google Scholar 

  19. Shafi G, Munshi A, Hasan TN, Alshatwi AA, Jyothy A, Lei DKY (2009) Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa. Cancer Cell Int 9:29

    Article  PubMed  Google Scholar 

  20. Mans DRA, Da Rocha BA (2000) Schwartsmann G. Anti-cancer drug discovery and development in Brazil: target plant as a rational strategy to acquire candidate anti-cancer compounds. The Oncologist 5:185–198

    Article  PubMed  CAS  Google Scholar 

  21. Khan MR, Mlungwana SM (1999) c-sitosterol, a cytotoxic sterol from Markhamia zanzibarica and Kigelia africana. Fitoterapia 70:96–97

    Article  CAS  Google Scholar 

  22. Panchal RG (1998) Novel therapeutic strategies to selectively kill cancer cells. Biochem Pharmacol 55:247–252

    Article  PubMed  CAS  Google Scholar 

  23. Ramos S (2007) Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem 18:427–442

    Article  PubMed  CAS  Google Scholar 

  24. Williams GT, Smith CA (1993) Molecular regulation of apoptosis: Genetic controls on cell death. Cell 74:777–779

    Article  PubMed  CAS  Google Scholar 

  25. Marzo I, Naval J (2008) Bcl-2 family members as molecular targets in cancer therapy. Biochem Pharmacol 76:939–946

    Article  PubMed  CAS  Google Scholar 

  26. Chang J, Hsu Y, Kuo P, Kuo Y, Chiang L, Lin C (2005) Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line. Life Sci 76:1883–1893

    Article  PubMed  CAS  Google Scholar 

  27. Mohammad R, Giri A, Goustin AS (2008) Small-molecule inhibitors of Bcl-2 family proteins as therapeutic agents in cancer. Recent Pat Anti-cancer Drug Discov 3:20–30

    Article  CAS  Google Scholar 

  28. Cha YY, Lee EO, Lee HJ, Park YD, Ko SG, Kim DH et al (2004) Methylene chloride fraction of Scutellaria barbata induces apoptosis in human U937 leukemia cells via the mitochondrial signaling pathway. Clin Chim Acta 348:41–48

    Article  PubMed  CAS  Google Scholar 

  29. Paris C, Bertoglio J, Breard J (2007) Lysosomal and mitochondrial pathways in milterfosine-induced apoptosis in U937 cells. Apoptosis 12:1257–1267

    Article  PubMed  CAS  Google Scholar 

  30. Han MH, Yoo YH, Choi YH (2008) Sanguinarine-induced apoptosis in human leukemia U937 cells via Bcl-2 downregulation and caspase-3 activation. Chemotherapy 54:157–165

    Article  PubMed  CAS  Google Scholar 

  31. Reed JC (1997) Double identity for proteins of the Bcl-2 family. Nature 387:773–776

    Article  PubMed  CAS  Google Scholar 

  32. Santen RJ, Song RX, McPherson R, Kumar R, Adam L, Jeng MH, Yue W (2002) The role of mitogen-activated protein (MAP) kinase in breast cancer. J Steroid Biochem Mol Biol 80:239–256

    Article  PubMed  CAS  Google Scholar 

  33. Motomura M, Kwon KM, Suh SJ, Lee YC, Kim YK, Lee IS (2008) Propolis induces cell cycle arrest and apoptosis in human leukemic U937 cells through Bcl-2/Bax regulation. Environ Toxicol Pharmacol 26:61–67

    Article  PubMed  CAS  Google Scholar 

  34. Sen S, D’Incalci M (1992) Biochemical events and relevance to cancer chemotherapy. FEBS Lett 307:122–127

    Article  PubMed  CAS  Google Scholar 

  35. Agarwal C, Sharma Y, Zhao J, Agarwal R (2000) A polyphenolic fraction from grape seeds causes irreversible growth inhibition of breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases activation and inducing G1 arrest and differentiation. Clin Cancer Res 6:2921–2930

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Biology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500016, Andhra Pradesh, India

    Gowhar Shafi, A. Jyothi & Anjana Munshi

  2. Dr. NTR University of Health Sciences, Vijayawada, Andhra Pradesh, India

    Gowhar Shafi & Anjana Munshi

  3. Molecular Cancer Biology Research Lab (MCBRL), Department of Food Sciences and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia

    Gowhar Shafi, Tarique N. Hasan, Naveed Ahmed Syed, Ali A. Alshatwi & Anjana Munshi

  4. Department of Botany and Microbiology, King Saud University, Riyadh, Saudi Arabia

    Amal A. Al-Hazzani

Authors
  1. Gowhar Shafi
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  2. Tarique N. Hasan
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  3. Naveed Ahmed Syed
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  4. Amal A. Al-Hazzani
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  5. Ali A. Alshatwi
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  6. A. Jyothi
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  7. Anjana Munshi
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Correspondence to Anjana Munshi.

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Shafi, G., Hasan, T.N., Syed, N.A. et al. Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer. Mol Biol Rep 39, 7373–7379 (2012). https://doi.org/10.1007/s11033-012-1569-0

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  • DOI: https://doi.org/10.1007/s11033-012-1569-0

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