Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation.
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.
Chiang
Chun-Te
CT
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Way
Tzong-Der
TD
Tsai
Shang-Jie
SJ
Lin
Jen-Kun
JK
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012991:Solanaceous Alkaloids / Q000737:chemistry / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014053:Tomatine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D004144:Diosgenin; D064429:Fatty Acid Synthases; D048031:JNK Mitogen-Activated Protein Kinases; D019308:Palmitic Acid; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D012991:Solanaceous Alkaloids; D058570:TOR Serine-Threonine Kinases; D014053:Tomatine; C003677:tomatidine; C546842:MTOR protein, human; C012037:solasodine