Premium
Diosgenin targets Akt‐mediated prosurvival signaling in human breast cancer cells
Author(s) -
Srinivasan Sowmyalakshmi,
Koduru Srinivas,
Kumar Raj,
Venguswamy Guhan,
Kyprianou Natasha,
Damodaran Chendil
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24419
Subject(s) - protein kinase b , diosgenin , cancer research , survivin , cyclin d1 , cyclin dependent kinase , estrogen receptor , cell growth , signal transduction , xiap , mapk/erk pathway , kinase , biology , apoptosis , pharmacology , chemistry , cell cycle , cancer , microbiology and biotechnology , medicine , breast cancer , programmed cell death , biochemistry , caspase , genetics
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, NF‐κB, 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. © 2009 UICC