Drier Climatic Conditions Increase Withanolide Content of Withania coagulans Enhancing Its Inhibitory Potential Against Human Prostate Cancer Cells
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Prostate cancer is one of the major causes of cancer-related deaths in men and there is a growing interest in identifying natural compounds for its management. We analyzed bioactive withanolides in Withania coagulans from 11 different sites in Pakistan and evaluated the antiprostate cancer activities of leaf extracts from two sites with the greatest amounts. Total withanolide concentration differed by ~ 17-fold between sites, ranging from 1.01 ± 0.01 mg/g dry weight (mean ± SE) at Jand to 16.83 ± 0.02 mg/g at Mohmand Agency. Different tissues varied in their total withanolide content with roots having the least (0.42 ± 0.07 mg/g dry weight) and leaves the most (2.45 ± 0.45 mg/g). We found strong inverse correlations between site annual precipitation versus withanolide amounts in fruits (r = − 0.84, P = 0.001), leaves (r = − 0.88, P < 0.001), roots (r = − 0.91, P < 0.001), and total (r = − 0.89, P < 0.001), but not stems (r = − 0.20, P = 0.556). Extracts made from Mianwali and Mohmand Agency leaves possessed high anticancer activity in terms of increased induction of apoptosis and decreased cell viability, cell proliferation, invasion, and migration of different prostate cancer cell lines. These results are useful for the selection of withanolide-rich germplasm with potent anticancer properties.
KeywordsProstate cancer Withania coagulans Withanolides Climatic conditions Ecotypes Anticancer properties
3-(45-Dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide
Mianwali leaf extract
Mohmand Agency leaf extract
High-performance liquid chromatography
Ultra-high performance liquid chromatography-mass spectrometry
The authors are very thankful to Dr. Hammad Ismail, Department of Biotechnology and Biochemistry for statistical help.
The Higher Education Commission of Pakistan provided funding for this research.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 7.Hoda, Q., Ahmad, S., Akhtar, M., Najmi, A. K., Pillai, K., & Ahmad, S. J. (2010). Antihyperglycaemic and antihyperlipidaemic effect of poly-constituents, in aqueous and chloroform extracts, of Withania coagulans Dunal in experimental type 2 diabetes mellitus in rats. Human & Experimental Toxicology, 29(8), 653–658.CrossRefGoogle Scholar
- 8.Chadha, Y. (1976). The wealth of India (ed ed.). New Delhi: Publication and Information Directorate CSIR.Google Scholar
- 9.Bharti, S. K., Kumar, A., Sharma, N. K., Krishnan, S., Gupta, A. K., & Padamdeo, S. R. (2012). Antidiabetic effect of aqueous extract of Withania coagulans flower in Poloxamer-407 induced type 2 diabetic rats. Journal of Medicinal Plants Research, 6, 5706–5713.Google Scholar
- 10.Kirthikar, K. R., & Basu, B. D. (1933). Indian medicinal plants (2nd ed.). Delhi: Bishen Singh Mahendra Pal Singh.Google Scholar
- 11.Dymock, W., Warden, C. J. H., & Hooper, D. (1893). Pharmacographia indica. In P. Kegan (Ed.), Trench. London: Trubner & Co..Google Scholar
- 12.Bown, D. (1995). Encyclopedia of herbs and their uses. London: Dorling Kindersley.Google Scholar
- 13.Chevallier, A. (1996). The encyclopedia of medicinal plants. London: Dorling Kindersley.Google Scholar
- 15.Mathur, D., & Agrawal, R. C. (2011). Evaluation of in vivo antimutagenic potential of fruits extracts of Withania coagulans. Der Pharma Chemica, 3, 373–376.Google Scholar
- 18.Hay, R. K. M., Waterman, P. G. (1993). Volatile oil crops: their biology, biochemistry, and production. In Longman Scientific & Technical (pp. 185). Harlow, Essex, England, New York, NY: J. Wiley.Google Scholar
- 20.Awasthi, D., Ram, H. K., & Misra, R. (2007). Evaluation of withanolide-A and withaferin-A in Withania somnifera (L.) Dunal (Ashwagandha) roots from different climatic zones of Madhya Pradesh. Indian Journal of Tropical Biodiversity, 15, 152–154.Google Scholar
- 22.Praveen, N., Naik, P. M., Manohar, S. H., & Murthy, H. N. (2010). Distribution of withanolide a content in various organs of Withania somnifera (L.) Dunal. International Journal of Pharma and Bio Sciences, 1, 1–5.Google Scholar
- 26.SAS Institute. (2013). SAS version 9.4. Cary: SAS Institute.Google Scholar
- 28.Levitt, J. (1980). Responses of plant to environmental stress: water, radiation, salt and other stresses. New York: Academic.Google Scholar
- 35.Ihsan-ul-Haq, Mirza, B., Kondratyuk, T. P., Park, E.-J., Burns, B. E., Marler, L. E., & Pezzuto, J. M. (2013). Preliminary evaluation for cancer chemopreventive and cytotoxic potential of naturally growing ethnobotanically selected plants of Pakistan. Pharmaceutical Biology, 51, 316–328.CrossRefGoogle Scholar
- 36.Senthil, V., Ramadevi, S., Venkatakrishnan, V., Giridharan, P., Lakshmi, B. S., Vishwakarma, R. A., & Balakrishnan, A. (2007). Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation. Chemico-Biological Interactions, 167(1), 19–30.CrossRefGoogle Scholar
- 38.Qureshi, S., Aziz, M. T., Qazi, M. H., & Saqib, T. (2015). Apoptotic activity of Withania coagulans methanolic extract in cancer cells using rats and HeLa cell line. Pakistan Journal of Medical and Health Sciences, 9, 123–127.Google Scholar