Osthole suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt/mTOR pathway.
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.
Lin
Victor Chia-Hsiang
VC
Department of Urology, E-Da Hospital, Department of Nursing, I-Shou University, Kaohsiung, Taiwan.
Chou
Chun-Hung
CH
Lin
Ying-Chao
YC
Lin
Jia-Ni
JN
Yu
Chien-Chih
CC
Tang
Chih-Hsin
CH
Lin
Hui-Yi
HY
Way
Tzong-Der
TD
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
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