Journal
PHYTOTHERAPY RESEARCH
Volume 25, Issue 12, Pages 1770-1775Publisher
WILEY-BLACKWELL
DOI: 10.1002/ptr.3441
Keywords
PANC-1 human pancreatic cancer; Vitex negundo; chrysoplenetin; chrysosplenol D; JFCR-39; COMPARE
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Funding
- Ministry of Health and Welfare for the Third-Term Comprehensive 10-Year Strategy for Cancer Control
- JSPS, Ministry of Education, Culture, Sports, Science and Technology, Japan
- Grants-in-Aid for Scientific Research [22240092, 221S0001, 22300342] Funding Source: KAKEN
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Human pancreatic cancer is known to be the most deadly disease with the lowest 5-year survival rate and is resistant to well known conventional chemotherapeutic drugs in clinical use. Screening of medicinal plants from Myanmar utilizing antiausterity strategy led to the identification of Vitex negundo as one of the medicinal plants having potent preferential cytotoxic activity against PANC-1 human pancreatic cancer cells. Bioactivity-guided phytochemical investigation led to the isolation of chrysoplenetin (1) and chrysosplenol D (2) as the active constituents with a PC(50) value of 3.4 mu g/mL and 4.6 mu g/mL, respectively, against PANC-1 cells. Both these compounds induced apoptosis-like morphological changes in PANC-1 cells. Chrysoplenetin was further tested against a panel of 39 human cancer cell lines (JFCR-39) at the Japanese Foundation for Cancer Research, and 25 cell lines belonging to lung, breast, CNS, colon, melanoma, ovarian, prostate cancer and stomach cancer cell lines were found to be highly sensitive to chrysoplenetin at a submicromolar range. In the JFCR-39 panel, lung NCI-H522, ovarian OVCAR-3 and prostate PC-3 cells were found to be most sensitive with GI(50) of 0.12, 0.18 and 0.17 mu M, respectively. The COMPARE analysis suggested that the molecular mode of action of chrysoplenetin was unique compared with the existing anticancer drugs. Copyright (C) 2011 John Wiley & Sons, Ltd.
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