An analog of withaferin a activates the MAPK and glutathione "stress" pathways and inhibits pancreatic cancer cell proliferation

Xiaobing Liu, Wenqing Qi, Laurence S. Cooke, E. M. Kithsiri Wijeratne, Ya Ming Xu, Marilyn T. Marron, A. A. Leslie Gunatilaka, Daruka Mahadevan

Research output: Contribution to journalArticle

10 Scopus citations

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. IC50 for 1, 2, and 3 were 0.87, 0.45, and 0.29 μM (BxPC-3); 1.28, 1.53, and 0.52 μM (MIAPaCa-2); and 0.59, 2.25, and 0.56 μM (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.

Original languageEnglish (US)
Pages (from-to)668-675
Number of pages8
JournalCancer Investigation
Volume29
Issue number10
DOIs
StatePublished - Nov 15 2011

Keywords

  • 4-Epi-withaferin A (2)
  • 427-Diacetyl-4-epi-withaferin A (3)
  • Apoptosis
  • Gene expression profiling
  • Glutathione pathway
  • MAPK
  • Pancreatic cancer
  • Withaferin A (1)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'An analog of withaferin a activates the MAPK and glutathione "stress" pathways and inhibits pancreatic cancer cell proliferation'. Together they form a unique fingerprint.

Cite this