The chemopreventive effect of withaferin A on spontaneous and inflammation-associated colon carcinogenesis models

Balaji Chandrasekaran, Deeksha Pal, Venkatesh Kolluru, Ashish Tyagi, Becca Baby, Nisha R. Dahiya, Khafateh Youssef, Houda Alatassi, Murali K. Ankem, Arun K. Sharma, Chendil Damodaran

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Chemopreventive effects and associated mechanisms of withaferin A (WA) against intestinal and colon carcinogenesis remain unknown. We investigated the chemopreventive effect of WA on transgenic adenomatous polyposis coli (APC Min/+) mouse and chemically induced azoxymethane/dextran sodium sulfate (AOM/DSS) models of intestinal and colon carcinogenesis. Oral WA administration (4 and 3 mg/kg) inhibited tumor initiation and progression of intestinal polyps formation in APC Min/+ mice and colon carcinogenesis in the AOM/DSS mouse model. WA-administered mice showed a significant reduction in both number [duodenum, 33% (P > 0.05); jejunum, 32% (P < 0.025); ileum, 43% (P < 0.001); and colon 59% (P < 0.01] and size of polyps in APC Min/+ mice compared with the respective controls. Similarly, tumor multiplicity was significantly reduced (P < 0.05) in the colon of WA-administered AOM/DSS mice. Pathological analysis showed reduced adenomas and tissue inflammation in WA-administered mouse models. Molecular studies suggested that WA inhibited the expression of inflammatory (interluekin-6, tumor necrosis factor-alpha and cyclooxygenase-2), pro-survival (pAKT, Notch1 and NF-? B) markers in APC Min/+ and AOM/DSS models. The results suggest that WA is a potent agent for preventing colon carcinogenesis and further investigation is required to show clinical utility of the agent.

Original languageEnglish (US)
Pages (from-to)1537-1547
Number of pages11
JournalCarcinogenesis
Volume39
Issue number12
DOIs
StatePublished - Dec 31 2018

All Science Journal Classification (ASJC) codes

  • Cancer Research

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