Egyptian Withania somnifera L., Chemotype and Comparative in vitro Cytotoxic Activity of Extracts and Isolated Withanolides

Aims: To investigate the chemotype of the Egyptian Withania somnifera and explore the cytotoxic activity of different extracts as well as the major isolated withanolides on four cell lines of common cancer variants in Egypt, both in vitro and using computational methods.

Study Design: Preparation of the different plant parts extract, determination of the chemotype of the Egyptian plant and bioactivity guided isolation of its major constituents.

Place and Duration of Study: Department of biochemistry, faculty of medicine and department of pharmacognosy, faculty of pharmacy between November 2014 and July 2016.

Methodology: We included four parts of the plant to be investigated on the four common cancer cell lines found in Egypt (liver, breast, lung and colon), in vitro MTT assay as well as docking analysis with the epidermal growth factor receptor identified as cancer molecular targets were performed, synergy analysis was carried on the most active withanolides.

Results: Roots extract showed selective cytotoxic activity against colon cancer cells while the 50% ethanolic extract of leaves showed selective inhibition against breast cancer cells. All investigated extracts and withanolides E, C and S showed cytotoxic activity against liver cancer cells with the highest activity manifested by the leaves extracts. Withanolide C showed anti-proliferative activity against breast cancer cells. The highest cytotoxic activity aganist HepG2 was observed for a combination of the active withanolides (E, C, and S) with IC50 value < 0.1 μg/ml.

Conclusion: Egyptian Withania somnifera is a subtype of chemotype III with different biological activity than the Indian one. Withanolides E, C and S might be a potential lead in the development of new anti-cancer treatment modalities.