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Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2‐overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation
Author(s) -
Chiang Chun-Te,
Way Tzong-Der,
Tsai Shang-Jie,
Lin Jen-Kun
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.021
Subject(s) - diosgenin , pi3k/akt/mtor pathway , protein kinase b , phosphorylation , fatty acid synthase , cancer research , apoptosis , chemistry , cancer cell , cancer , biology , fatty acid , biochemistry , medicine , organic chemistry
Fatty acid synthase (FAS) expression is markedly elevated in HER2‐overexpressing breast cancer cells. In this study, diosgenin, a plant‐derived steroid, was found to be effective in suppressing FAS expression in HER2‐overexpressing breast cancer cells. Diosgenin preferentially inhibited proliferation and induced apoptosis in HER2‐overexpressing cancer cells. Furthermore, diosgenin inhibited the phosphorylation of Akt and mTOR, and enhanced phosphorylation of JNK. The use of pharmacological inhibitors revealed that the modulation of Akt, mTOR and JNK phosphorylation was required for diosgenin‐induced FAS suppression. Finally, we showed that diosgenin could enhance paclitaxel‐induced cytotoxicity in HER2‐overexpressing cancer cells. These results suggested that diosgenin has the potential to advance as chemopreventive or chemotherapeutic agent for cancers that overexpress HER2.