Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer cells

Sowmyalakshmi Srinivasan, Srinivas Koduru, Raj Kumar, Guhan Venguswamy, Natasha Kyprianou, Chendil Damodaran

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

In recent years, Akt signaling has gained recognition for its functional role in more aggressive, therapy-resistant malignancies. As it is frequently constitutively active in cancer cells, several drugs are being investigated for their ability to inhibit Akt signaling. The purpose of this study is to determine effect of diosgenin (fenugreek), a dietary compound on Akt signaling and its downstream targets on estrogen receptor positive (ER+) and estrogen receptor negative (ER-) breast cancer (BCa) cells. Diosgenin inhibits pAkt expression and Akt kinase activity without affecting PI3 kinase levels, resulting in the inhibition of its downstream targets, NFκB, Bcl-2, survivin and XIAP. The Raf/MEK/ERK pathway, another functional downstream target of Akt, was inhibited by diosgenin in ER+ but not in ER- BCa cells. Additionally, we found that diosgenin caused G1 cell cycle arrest by downregulating cyclin D1, cdk-2 and cdk-4 expression in both ER+ and ER- BCa cells resulting in the inhibition of cell proliferation and induction of apoptosis. Interestingly, no significant toxicity was seen in the normal breast epithelial cells (MCF-10A) following treatment with diosgenin. Additionally, in vivo tumor studies indicate diosgenin significantly inhibits tumor growth in both MCF-7 and MDA-231 xenografts in nude mice. Thus, these results suggest that diosgenin might prove to be a potential chemotherapeutic agent for the treatment of BCa.

Original languageEnglish (US)
Pages (from-to)961-967
Number of pages7
JournalInternational Journal of Cancer
Volume125
Issue number4
DOIs
StatePublished - Aug 15 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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