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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signaling.

Abstract Source:

PLoS One. 2010;5(10):e13536. Epub 2010 Oct 21. PMID: 20975835

Abstract Author(s):

Nashi Widodo, Didik Priyandoko, Navjot Shah, Renu Wadhwa, Sunil C Kaul

Article Affiliation:

National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.

Abstract:

BACKGROUND AND PURPOSE: Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways.

METHODOLOGY/PRINCIPAL FINDINGS: Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress.

CONCLUSION: Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy.

Study Type : In Vitro Study

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Sayer Ji
Founder of GreenMedInfo.com

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Depression: 21st Century Solutions + The Dark Side of Wheat

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