Selective killing of cancer cells by leaf extract of Ashwagandha: components, activity and pathway analyses

Cancer Lett. 2008 Apr 8;262(1):37-47. doi: 10.1016/j.canlet.2007.11.037. Epub 2008 Jan 10.


Ashwagandha, also called as "Queen of Ayurveda" and "Indian ginseng", is a commonly used plant in Indian traditional medicine, Ayurveda. Its roots have been used as herb remedy to treat a variety of ailments and to promote general wellness. However, scientific evidence to its effects is limited to only a small number of studies. We had previously identified anti-cancer activity in the leaf extract (i-Extract) of Ashwagandha and demonstrated withanone as a cancer inhibitory factor (i-Factor). In the present study, we fractionated the i-Extract to its components by silica gel column chromatography and subjected them to cell based activity analyses. We found that the cancer inhibitory leaf extract (i-Extract) has, at least, seven components that could cause cancer cell killing; i-Factor showed the highest selectivity for cancer cells and i-Factor rich Ashwagandha leaf powder was non-toxic and anti-tumorigenic in mice assays. We undertook a gene silencing and pathway analysis approach and found that i-Extract and its components kill cancer cells by at least five different pathways, viz. p53 signaling, GM-CFS signaling, death receptor signaling, apoptosis signaling and G2-M DNA damage regulation pathway. p53 signaling was most common. Visual analysis of p53 and mortalin staining pattern further revealed that i-Extract, fraction F1, fraction F4 and i-Factor caused an abrogation of mortalin-p53 interactions and reactivation of p53 function while the fractions F2, F3, F5 work through other mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle
  • Cell Line, Tumor
  • Genes, Plant
  • Genes, p53
  • Humans
  • Medicine, Ayurvedic
  • Mice
  • Neoplasms / drug therapy*
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • Plant Leaves*
  • Signal Transduction / drug effects
  • Withania*


  • Antineoplastic Agents
  • Plant Extracts
  • Ashwagandha