原创力文档selective killing of cancer cells by ashwagandha leaf extract and its component withanone involves ros signaling选择性地杀死癌细胞ashwagandha叶提取物及其组件withanone涉及ros信号.pdfVIP
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selective killing of cancer cells by ashwagandha leaf extract and its component withanone involves ros signaling选择性地杀死癌细胞ashwagandha叶提取物及其组件withanone涉及ros信号
Selective Killing of Cancer Cells by Ashwagandha Leaf
Extract and Its Component Withanone Involves ROS
Signaling
1,2 1,3 1,3 1 1
Nashi Widodo , Didik Priyandoko , Navjot Shah , Renu Wadhwa *, Sunil C. Kaul *
1 National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan, 2 Department of Biology, Faculty of Mathematics and Natural Sciences,
Brawijaya University, Malang, Indonesia, 3 Graduate School of Life and Environmental Sciences, University of Tsukuba, 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 unde
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