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  • Title: An analog of withaferin A activates the MAPK and glutathione "stress" pathways and inhibits pancreatic cancer cell proliferation.
    Author: Liu X, Qi W, Cooke LS, Kithsiri Wijeratne EM, Xu YM, Marron MT, Leslie Gunatilaka AA, Mahadevan D.
    Journal: Cancer Invest; 2011 Dec; 29(10):668-75. PubMed ID: 22085270.
    Abstract:
    Withaferin A (WA) (1) and two analogs [4-epi-withaferin A (2) and 4,27-diacetyl-4-epi-withaferin A (3)] were evaluated for antitumor activity in pancreatic cancer cells. IC(50) for 1, 2, and 3 were 0.87, 0.45, and 0.29 ?M (BxPC-3); 1.28, 1.53, and 0.52 ?M (MIAPaCa-2); and 0.59, 2.25, and 0.56 ?M (PANC-1), respectively. We chose WA analog 3 for functional studies with confirmatory RT-PCR and Western blotting. ANOVA identified 33 (MIAPaCa-2), 54 (PANC-1), and 48 (BxPC-3) gene expression changes. Fisher exact test demonstrated MAPK and glutathione pathways to be overexpressed with WA analog 3. WA analog 3 elicits a dose- and time-dependent apoptosis, activates MAPK and glutathione ?stress? pathways, and inhibits proliferation.
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