title: Effect of dapagliflozin on colon cancer cell [Rapid Communication].
abstract: Dapagliflozin is a SGLT2 (Sodium/Glucose cotransporter 2) inhibitor that reduces circulating glucose levels in type 2 diabetic patients by blocking the SGLT2-dependent reabsorption of glucose in the kidney. Dapagliflozin is metabolized by UGT1A9 (UDP Glucuronosyltransferase 1 family, Polypeptidase A9), suppressing its SGLT2 inhibitor activity. However little information is available on whether dapagliflozin acts in the absence of dapagliflozin metabolism. Treatment with 0.5μM dapagliflozin significantly reduced the number of HCT116 cells, which express SGLT2 but not UGT1A9. This was independent of SGLT2 inhibition, as the SGLT2 inhibitor phlorizin had no effect. Dapagliflozin also enhanced Erk phosphorylation but without changing levels of uncleaved and cleaved PPAR and uncleaved caspase-3, suggesting that the cause of the decrease in HCT116 cell number was apoptosis independent cell death. Taken together, these data indicate a new potential role for dapagliflozin as an anticancer reagent in tumor cell populations that do not express UGT1A9.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan.
authors.forename: Tsugumichi
authors.initials: T
authors.lastname: Saito
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Eijiro
authors.initials: E
authors.lastname: Yamada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Aya
authors.initials: A
authors.lastname: Osaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tagaya
authors.forename: Ryo
authors.initials: R
authors.lastname: Shibusawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Okada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D002452:Cell Count; D003110:Colonic Neoplasms / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005960:Glucosides / Q000378:metabolism / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D000970:Antineoplastic Agents; D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C000715591:UGT1A9 protein, human; C529054:dapagliflozin; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9