Selective killing of cancer cells by leaf extract of Ashwagandha: components, activity and pathway analyses.
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.
Widodo
Nashi
N
National Institute of Advanced Industrial Science & Technology (AIST), Central, Higashi, Tsukuba, Ibaraki, Japan.
Takagi
Yasuomi
Y
Shrestha
Bhupal G
BG
Ishii
Tetsuro
T
Kaul
Sunil C
SC
Wadhwa
Renu
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D017343:Genes, Plant; D016158:Genes, p53; D006801:Humans; D008515:Medicine, Ayurvedic; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D015398:Signal Transduction / Q000187:drug effects; D032341:Withania
D000970:Antineoplastic Agents; D010936:Plant Extracts; C030693:Ashwagandha