A critical review of anticancer properties of Withania somnifera (L.) Dunal with respect to the biochemical mechanisms of its phytochemical constituents

U R Surya,N Praveen,P M Naik,U Vinayak

doi:10.14719/pst.2021.8.2.969

Abstract

Cancer is a leading cause of mortality worldwide, the conventional chemotherapeutic drugs have been known for their toxicity and numerous side effects. A new approach to treat cancer involves phytochemical drugs. In the present review, anti-cancer activity of a class of steroidal lactones called withanolides obtained from Withania somnifera (L.) Dunal is discussed. The commonly studied bioactive compounds namely withaferin-A, withanoside IV, withanoside VI and withanolide-A among others obtained from methanolic and chloroform extract of the leaves and various alcoholic, aqueous and chloroform extract of roots have shown inhibition to various human cancer cell lines including skin, breast, colon, prostate, liver, ovary, cervical and lung. Prominent mechanisms of action include induction of apoptosis by NOS upregulation, ROS production and NBS2 or COX-2 inhibition; cytotoxicity by humoral and cell mediated immune response, activation of p53 and pRB and inhibition of various viral oncoproteins; cell cycle arrest by Cdc2 facilitated mitotic catastrophe, cyclin-D1 down-regulation and inhibition of transcription factors. Cancers are also controlled by inhibition of angiogenesis and metastasis of the tumor cells. In addition to anti-tumorogenic properties, W. somnifera also holds properties that make it a potential adjuvant in integrated cancer therapeutics and in enhancing the effectiveness of ongoing radiation therapy.

Highlights

One of the most common forms of medication involves phytotherapy; plants show a vast molecular diversity and produce numerous therapeutic phytochemicals
Anti-cancer activity of a class of steroidal lactones called withanolides obtained from Withania somnifera (L.) Dunal is discussed
The commonly studied bioactive compounds namely withaferin-A, withanoside IV, withanoside VI and withanolide-A among others obtained from methanolic and chloroform extract of the leaves and various alcoholic, aqueous and chloroform extract of roots have shown inhibition to various human cancer cell lines including skin, breast, colon, prostate, liver, ovary, cervical and lung

Summary

Introduction

One of the most common forms of medication involves phytotherapy; plants show a vast molecular diversity and produce numerous therapeutic phytochemicals. A study conducted on CaSKi cell line of human cervical cancer has found withaferin-A to possess the ability to downregulate oncoproteins E6 and E7 expression by HPV This induces accumulation of p53 in tumor cells and upregulation of p21 cip1/waf, which in turn interact with proliferating cell nuclear antigen (PCNA), leading to B1, p34 cdc and PCNA levelsmodulated-G2/M-cell-cycle-arrest. Another known mechanism of cervical cancer inhibition by withaferin-A includes phosphorylation of Tyr-705 and Ser-727 and STAT 3, all of which lead to altered expression of BCl 2, Bax, Caspase 2 and cleaved PARP, which are p53 mediated apoptosis markers.

Conclusion and Future perspectives

Findings

Conflict of interests