title: Osthole suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt/mTOR pathway.
abstract: While fatty acid synthase (FASN) has been shown to be expressed in many human solid tumors, FASN has also been identified in preneoplastic lesions. HER2, which has also been identified in preneoplastic breast lesions, has been shown to upregulate FASN expression. Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a traditional Chinese medicine, was found to be effective in suppressing FASN expression in HER2-overexpressing breast cells. Osthole preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Moreover, osthole inhibited the phosphorylation of Akt and mTOR. The use of Akt-overexpression revealed that the modulation of Akt and mTOR was required for osthole-induced FASN suppression. Finally, we showed that osthole could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells. These results suggested that osthole has the potential to advance as chemopreventive or chemotherapeutic agent for cancers that overexpress HER2.
authors.affiliation: Department of Urology, E-Da Hospital, Department of Nursing, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Victor Chia-Hsiang
authors.initials: VC
authors.lastname: Lin
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Lin
authors.forename: Jia-Ni
authors.initials: JN
authors.lastname: Lin
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Yu
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018734:Genes, erbB-2; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
chemical_list: D003374:Coumarins; D047908:Intracellular Signaling Peptides and Proteins; D064429:Fatty Acid Synthases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C046627:osthol