Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation.

Abstract

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.

• Authors: Chun-Te Chiang, Tzong-Der Way, Shang-Jie Tsai, Jen-Kun Lin
• Journal: FEBS letters (FEBS Lett) Vol. 581 Issue 30 Pg. 5735-42 (Dec 22 2007) ISSN: 0014-5793 [Print] England
• PMID: 18022396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phosphoproteins
• Protein Kinase Inhibitors
• Solanaceous Alkaloids
• tomatidine
• Palmitic Acid
• Tomatine
• Fatty Acid Synthases
• Protein Kinases
• MTOR protein, human
• Receptor, ErbB-2
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• JNK Mitogen-Activated Protein Kinases
• Diosgenin
• solasodine

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (enzymology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diosgenin (chemistry, pharmacology)
• Down-Regulation (drug effects)
• Drug Screening Assays, Antitumor
• Fatty Acid Synthases (biosynthesis, genetics)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Palmitic Acid (pharmacology)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Protein Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, ErbB-2 (genetics, metabolism)
• Solanaceous Alkaloids (chemistry, pharmacology)
• TOR Serine-Threonine Kinases
• Tomatine (analogs & derivatives, chemistry, pharmacology)
• Up-Regulation (drug effects)