Vitex rotundifolia fractions induce apoptosis in human breast cancer cell line, MCF-7, via extrinsic and intrinsic pathways

Gul-e-Saba Chaudhry , Rehmat Jan, Habsah Mohamad, Tengku Sifzizul Tengku Muhammad

Abstract


Breast cancer is amongst frequently diagnosed cancer type throughout the world. Due to reduced efficacy of current chemotherapeutics, several natural products have been screened for better alternatives. The cytotoxic activity of fractions prepared from leaves extract of Vitex rotundifolia (V. rotundifolia) on human breast cancer cell line, MCF-7 was studied. The fractions F1, F2, F3, and F5 of V. rotundifolia produced concentration-dependent cytotoxic effects on MCF-7 cell line. The relative potential of cytotoxicity of the fractions on MCF-7 cell line was found to be F3 > F2 > F5 > F1. The active fractions induce apoptosis in MCF-7 cell line determined by annexin V base assay. The phosphatidylserine externalization and the presence of DNA fragmentation in treated cells confirms the early and late apoptosis in treated cells.The V. rotundifolia fractions induced apoptosis by both pathways; extrinsic pathways via activation of caspase-8 and intrinsic pathways through enhanced bax/bcl-2 ratio and activation of caspase-3/7 and caspase-9 proapoptotic proteins. Furthermore, chemical profiling indicates various phenolic, flavonoids, and terpenoids compounds in the active fractions. Thus, V. rotundifolia might be a suitable candidate to investigate further and develop molecular targeted cancer therapeutics by understanding the fundamental mechanisms involved in the regulation of cell death in cancer cells. 


Keywords


Apoptosis; Breast cancer; Caspases; DNA fragmentation, Vitex rotundifolia.

Full Text:

PDF

References


REFERENCES

Weir HK, Anderson RN, Coleman King SM, Soman A, Thompson TD, Hong Y, et al. Heart disease and cancer deaths-trends and projections in the United States, 1969-2020. Prev Chron Dis. 2016;13:E157.

Garbi MI, Osman EE, Kabbashi AS, Saleh MS, Yuosof YS, Mahmoud SA, et al. Cytotoxicity of Vitex trifolia leaf extracts on MCF-7 and Vero cell lines. J Sci Innov Res. 2015;4(2):89-93.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.

Leon Guerrero RT, Novotny R, Wilkens LR, Chong M, White KK, Shvetsov YB, et al. Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan. Cancer Epidemiol. 2017;50(Pt B):221-233.

Desai AG, Qazi GN, Ganju RK, El-Tamer M, Singh J, Saxena AK, et al. Medicinal plants and cancer chemoprevention. Curr Drug Metab. 2008;9(7):581-591.

Wachtel-Galor S, Benzie IFF. Herbal Medicine: An Introduction to Its History, Usage, Regulation, Current Trends, and Research Needs. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and clinical aspects. 2nd ed. Boca Raton (FL): CRC Press/Taylor and Franscis; 2011. pp: 1-10.

Valli M, Pivatto M, Danuello A, Castro-Gamboa Ian, Silva DHS, Cavalheiro AJ, et al. Tropical biodiversity: has it been a potential source of secondary metabolites useful for medicinal chemistry? Quím Nova. 2012;35(11):2278-2287.

Meena AK, Niranjan US, Rao MM, Padhi MM, Babu R. A review of the important chemical constituents and medicinal uses of Vitex genus. Asian J Tradit Med. 2011;6 (2):54-60.

Ono M, Yanaka T, Yamamoto M, Ito Y, Nohara T. New diterpenes and norditerpenes from the fruits of Vitex rotundifolia. J Nat Prod. 2002;65(4):537-541.

Hu Y, Zhang Q, Xin H, Qin LP, Lu BR, Rahman K, et al. Association between chemical and genetic variation of Vitex rotundifolia populations from different locations in China: its implication for quality control of medicinal plants. Biomed Chromatogr. 2007;21(9):967-975.

Kim DK. Antioxidative constituents from the twigs of Vitex rotundifolia. Biomol Ther. 2009;17(4):412-417.

Yoshiokaa T, Inokuchib T, Fujiokac S, Kimurab Y. Phenolic compounds and flavonoids as plant growth regulators from fruit and leaf of Vitex rotundifolia. Z Naturforsch C. 2004;59(7-8):509-514.

Iwashina T, Setoguchi H, Kitajima J. Flavonoids from the leaves of Vitex rotundifolia (Verbenaceae), and their qualitative and quantitative comparison between coastal and inland populations. Bull Natl Mus Nat Sci Ser B. 2011;37(2):87-94.

Ono M, Yamamoto M, Masuoka C, Ito Y, Yamashita M, Nohara T. Diterpenes from the fruits of Vitex rotundifolia. J Nat Prod. 1999;62(11):1532-1537.

Hudaya T, Gul-e-Saba, Taib M, Ismail N, Mohammad TST. Methanol extracts of four selected marine sponges induce apoptosis in human breast cancer cell line, MCF-7. Int J Res Pharm Sci. 2017;8(4):667-675.

Gul-e-Saba, Islamiah M, Ismail N, Mohamad H, Sung YY, Muhammad TST. Induction of apoptosis by Aaptos sp., fractions in human breast cancer line, MSF-7. Int J Res Pharm Sci. 2017;9(2):328-337.

Vijayarathna S, Sasidharan S. Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines. Asian Pac J Trop Biomed. 2012;2(10):826-829.

Fadok VA, Bratton DL, Frasch SC, Warner ML, Henson PM. The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death Differ.1998;5(7):551-562.

Collins JA, Schandl CA, Young KK, Vesely J, Willingham MC. Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem. 1997;45(7):923-934.

Jan R, Chaudhry GS. Understanding apoptosis and apoptotic pathway targeted cancer therapeutics. Adv Pharm Bull. 2019. In press.

Song HM, Park GH, Park SB, Kim HS, Son HJ, Um Y, et al. Vitex rotundifolia fruit suppresses the proliferation of human colorectal cancer cells through down-regulation of cyclin D1 and CDK4 via proteasomal-dependent degradation and transcriptional inhibition. Am J Chin Med. 2018;46(1):191-207.

Xin H, Kong Y, Wang Y, Zhou Y, Zhu Y, Li D, et al. Lignans extracted from Vitex negundo possess cytotoxic activity by G2/M phase cell cycle arrest and apoptosis induction. Phytomedicine. 2013;20(7):640-647.

Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 2013;14:32-40.

Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 2002;9(3):459-470.

Ohyama K, Akaike T, Imai M, Toyoda H, Hirobe C, Bessho T. Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress. Int J Biochem Cell Biol. 2005;37(7):1496-1510.

Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, et al. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds. PLoS One. 2013;8(2):e56643.

Mc Gee MM, Hyland E, Campiani G, Ramunno A, Nacci V, Zisterer DM. Caspase-3 is not essential for DNA fragmentation in MCF-7 cells during apoptosis induced by the pyrrolo-1,5-benzoxazepine, PBOX-6. FEBS Lett. 2002;515(1-3):66-70.

Kim R. Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer. 2005;103(8):1551-1560.

Wang Q, Zhang L, Yuan X, Ou Y, Zhu X, Cheng Z, et al. The relationship between the Bcl-2/Bax proteins and the mitochondria-mediated apoptosis pathway in the differentiation of adipose-derived stromal cells into neurons. PLoS One. 2016;11(10):e0163327.

Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005;55(3):178-194.

Wang HY, Cai B, Cui CB, Zhang DY, Yang BF. Vitexicarpin, a flavonoid from Vitex trifolia L., induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway. Yao Xue Xue Bao. 2005;40(1):27-31.

Peng CC, Chyau CC, Wang HE, Chang CH, Chen KC, Kuang-Yu Chou, et al. Cytotoxicity of ferulic acid on T24 cell line differentiated by different microenvironments. Biomed Res Int. 2013;2013. Article ID: 579859.

LinY, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potentials for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634-646.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.