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

Chun-Te Chiang; Tzong-Der Way; Shang-Jie Tsai; Jen-Kun Lin

doi:10.1016/j.febslet.2007.11.021

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

FEBS Lett. 2007 Dec 22;581(30):5735-42. doi: 10.1016/j.febslet.2007.11.021. Epub 2007 Nov 20.

Authors

Chun-Te Chiang¹, Tzong-Der Way, Shang-Jie Tsai, Jen-Kun Lin

Affiliation

¹ Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

PMID: 18022396
DOI: 10.1016/j.febslet.2007.11.021

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Breast Neoplasms / enzymology*
Cell Line, Tumor
Cell Proliferation / drug effects
Diosgenin / chemistry
Diosgenin / pharmacology*
Down-Regulation / drug effects
Drug Screening Assays, Antitumor
Fatty Acid Synthases / biosynthesis
Fatty Acid Synthases / 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
Receptor, ErbB-2 / metabolism*
Solanaceous Alkaloids / chemistry
Solanaceous Alkaloids / pharmacology
TOR Serine-Threonine Kinases
Tomatine / analogs & derivatives
Tomatine / chemistry
Tomatine / pharmacology
Up-Regulation / drug effects

Substances

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