Journal: Molecules

Article Title: Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity

doi: 10.3390/molecules25030495

Figure Lengend Snippet: Relative sensitivities of HCT116 and HepG2 cells to dapagliflozin treatment. ( a ) Time-course effects of dapagliflozin treatment on HCT116 cell morphology and cell attachment. The HCT116 cells were treated with vehicle (DMSO) or 0.5 mM dapagliflozin for the times indicated. Please note that 25 min treatment with 0.5 mM dapagliflozin let HCT116 cells be lifted off the dish as a sheet and flipped over onto the side of the plate, as indicated by the arrow. This phenomenon suggested us that the cell attachment was impaired by dapagliflozin treatment. Phase-contrast microscopy images (×100 magnification) are presented. These experiments were conducted in triplicate, and the typical results are shown. ( b ) ( left panel ) HCT116 cells were treated with either vehicle (DMSO) or 0.125, 0.25, 0.5, 1.0, or 2.0 mM dapagliflozin for 35 min. The experiments were conducted independently in triplicate, and typical results are presented (×100 magnification). ( b ) ( right panel ) HepG2 cells were treated with either vehicle (DMSO) or 0.125, 0.25, 0.5, 1.0, or 2.0 mM dapagliflozin for 35 min. The experiments were conducted independently in triplicate, and typical results are presented (×100 magnification). ( c ) Effect of dapagliflozin on HCT116, HepG2, PANC-1, and H1792 cells were quantified and presented as a bar graph. The Y -axis represents the amounts of cells attached to the culture well and the X -axis represents the concentration of dapagliflozin added to the culture medium (n = 3, in each column, 0 mM vs. 0.125 mM; not significant, 0 mM vs. 0.25 mM; * p < 0.01, 0 mM vs. 0.5, 1.0, 2.0 mM; ** p < 0.001). ( d ) Effect of empagliflozin on HCT116, HepG2, PANC-1, and H1792 cells were quantified and presented as a bar graph. The Y -axis represents the amounts of cells attached to the culture well and the X -axis represents the concentration of empagliflozin added to the culture medium (n = 3). ( e ) Effect of tofogliflozin on HCT116, HepG2, PANC-1, and H1792 cells were quantified and presented as a bar graph. The Y -axis represents the amounts of cells attached to the culture well and the X -axis represents the concentration of tofogliflozin added to the culture medium (n = 3).

Article Snippet: Dapagliflozin (CS-0781), empagliflozin (AG-CR1-3619-M-010), and tofogliflozin (CS-3793), antibody recognizing DDR1 (GTX111453), were purchased from Funakoshi Co., Ltd (Tokyo, Japan).

Techniques: Cell Attachment Assay, Microscopy, Concentration Assay

Journal: Molecules

Article Title: Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity

doi: 10.3390/molecules25030495

Figure Lengend Snippet: Clinical cases-Patients with type 2 diabetes mellitus and cancer were treated by sodium-glucose cotransporter 2 (SGLT2) inhibitor. ( a ) Clinical cases – Patients with type 2 diabetes mellitus and cancer treated by SGLT2 inhibitors. Six cases were demonstrated in this research. Cases 1 and 2 concern patients associated with colon cancer and type 2 diabetes mellitus. The CEA changes are presented in a line graph; chemotherapy, radiation therapy, and dapagliflozin administration are represented by black arrows ( a, case 1 and 2). In case 2, there was a period where in the patient was treated with dapagliflozin alone, and the CEA level declined. However, the CEA level started to rise after the cessation of dapagliflozin. In this patient, tofogliflozin combined with radiation therapy did not show a good effect. Cases 3 and 4 concern patients associated with pancreatic cancer and type 2 diabetes mellitus. The CA19-9 changes are presented in a line graph; chemotherapy and dapagliflozin administration are represented by black arrows ( a, case 3 and 4). Case 5 is a patient associated with liver cancer and type 2 diabetes mellitus. The PIVKAII changes are presented as a line graph; chemotherapy and dapagliflozin administration are represented by black arrows ( a, case 5). Case 6 is a patient associated with lung cancer (squamous cell carcinoma; patient experienced three separate recurrences despite dapagliflozin administration) and type 2 diabetes mellitus. The CYFRA changes are presented in a line graph; chemotherapy and dapagliflozin administration are represented by black arrows ( a, case 6). ( b ) Immunohistochemical analysis. The SGLT2 and UGT1A9 staining results of cases 1 and 2 are shown in b. Immunostaining was performed as reported previously (16). In both cases, SGLT2 was stained well in cancer cells, but UGT1A9 was not. Please note that the material of case 1 was obtained by biopsy and the material of case 2 was obtained b.

Article Snippet: Dapagliflozin (CS-0781), empagliflozin (AG-CR1-3619-M-010), and tofogliflozin (CS-3793), antibody recognizing DDR1 (GTX111453), were purchased from Funakoshi Co., Ltd (Tokyo, Japan).

Techniques: Immunohistochemical staining, Staining, Immunostaining