title: Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.
abstract: Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan k.nishi@hamayaku.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Nishi
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Sawamoto
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Tokizawa
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwase
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
authors.forename: Nagahiko
authors.initials: N
authors.lastname: Yumita
authors.affiliation: Laboratory of Drug Metabolism and Pharmacotherapeutics, Department of Clinical Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D017304:Annexin A5 / Q000737:chemistry; D017209:Apoptosis; D002224:Carbanilides / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002569:Cerulenin / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000096:biosynthesis*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D019308:Palmitic Acid / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D017304:Annexin A5; D002224:Carbanilides; D005227:Fatty Acids; D008055:Lipids; D002569:Cerulenin; D019308:Palmitic Acid; D064429:Fatty Acid Synthases; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; C005055:cloflucarban
keywords: TOFA; apoptosis; fatty acid synthesis; pancreatic cancer