Identifying and understanding the pathways for anti-cancer properties of natural plant extracts rich in flavonoid compounds

Summary of the project:
Cancer has been one of the major causes for morbidity globally. There is a constant demand for new therapies that are more specific with less toxic side effects. Most of the anti-cancer drugs used clinically so far are natural products extracted from trees and plants. Majority of these compounds have cytotoxic effects that arrest the cells in mitosis, acting as anti-mitotic drugs ( Jordan and Wilson, 2004) . Mitotic arrest induced by anti-mitotic drugs can cause cell death or apoptosis or p53, an onco suppressor protein dependent cell cycle arrest (Orth et al., 2011) . In any case, upon treatments with anti-mitotic drugs cells stop dividing, preventing growth of cancerous cells or tumorigenesis. This physiological characteristic of cells has allowed the use of anti-mitotic drugs as anti-cancer therapeutic tools. Nepal’s varied geographical status is favorable for several medicinal herbs that are rich in compounds that may have anti-cancer effects. Here, we propose to study the anti-mitotic and anti-cancer effects of medicinal herbs available in Nepal that are rich in flavonoid contents. Flavonoids are phenolic substances with significant antioxidant and chelating properties, whose major sources are plants, fruits, and vegetables ( Heim et al., 2002) (Pietta, 2000) . Due to antioxidant and chelating properties, flavonoids are used for broad spectrum pharmacological activities such as vasodilating and anti-cancer agents. Studies have shown a positive correlation between a long-term consumption of a flavonoids-rich diet and lower risk of colon, prostate and breast cancers (Batra and Sharma, 2013) . However, it is not clear the precise mechanism how flavonoids show anti-cancer effects. Our preliminary results identified a few herbs that are rich in flavonoid contents as determined by Alkaline reagent test and Schinoda test. We plan to use methanolic extracts of these herbs as a source for flavonoids and evaluate whether these extracts have dose dependent cytotoxic effects on transformed cells lines. If they have cytotoxic effects, we will further study for any cell cycle or microtubule dynamics dependent mechanism that may involve cytotoxicity of cells. Moreover, we will examine the specificity of cytotoxicity in transformed versus non-transformed cells.

Funding body: The World Academy of Sciences
Funding year: 2019
Principal Investigator: Jivan Shakya, PhD., Center for Health and Disease Studies Nepal (CHDS-Nepal)
Co-Principal Investigators: Prof. Rajani Malla and Pragati Pradhan, MSc., Center Department of Biotechnology, TU.
Advisor: Roshan Lal Shrestha, Ph.D., Center for Health and Disease Studies Nepal (CHDS-Nepal)
Status: Ongoing
Publication: Not Yet