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.
journal_name
Cancer Investjournal_title
Cancer investigationauthors
Liu X,Qi W,Cooke LS,Kithsiri Wijeratne EM,Xu YM,Marron MT,Leslie Gunatilaka AA,Mahadevan Ddoi
10.3109/07357907.2011.626478subject
Has Abstractpub_date
2011-12-01 00:00:00pages
668-75issue
10eissn
0735-7907issn
1532-4192journal_volume
29pub_type
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