Open Access

Dapagliflozin induces apoptosis by downregulating cFILPL and increasing cFILPS instability in Caki‑1 cells

  • Authors:
    • Ji Hoon Jang
    • Tae-Jin Lee
    • Eon-Gi Sung
    • In-Hwan Song
    • Joo-Young Kim
  • View Affiliations

  • Published online on: September 22, 2022     https://doi.org/10.3892/ol.2022.13521
  • Article Number: 401
  • Copyright: © Jang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Dapagliflozin is a sodium/glucose cotransporter 2 inhibitor used recently to treat patients with type 2 diabetes. A recent study has demonstrated that dapagliflozin induces apoptosis in human renal and breast tumor cells. However, to the best of our knowledge, the molecular mechanism underlying dapagliflozin‑mediated apoptosis in Caki‑1 human renal carcinoma cells has not been elucidated. The present study demonstrated that the dapagliflozin treatment dose‑dependently increased cell death in Caki‑1 cells. Dapagliflozin treatment also induced apoptosis as confirmed by FITC‑conjugated Annexin V/PI staining. Additionally, treatment with dapagliflozin reduced the expression levels of anti‑apoptotic proteins, cellular Fas‑associated death domain‑like interleukin‑1‑converting enzyme‑inhibitory protein (cFLIP)L and cFLIPS in Caki‑1 cells. Benzyloxycarbonyl‑Val‑Ala‑Asp‑fluoromethyl‑ketone inhibited dapagliflozin‑induced apoptosis, implying that dapagliflozin‑­induced apoptosis is regulated by a caspase‑dependent pathway. By contrast, N‑acetylcysteine had no effect on dapagliflozin‑­induced apoptosis and downregulation of cFLIPL and cFLIPS expression. Furthermore, overexpression of cFLIPL, but not cFLIPS, partially inhibited apoptosis induced by dapagliflozin. cFLIPL and cFLIPS mRNA levels remained constant in Caki‑1 cells after treatment with 0, 20, 40, 60, 80 and 100 µM dapagliflozin. Notably, it was confirmed that cFLIPS protein levels were reduced due to the increased cFLIPS instability in dapagliflozin‑treated Caki‑1 cells. The present study also demonstrated that dapagliflozin had no effect on HK‑2 normal human kidney cells. Taken together, the present study revealed that dapagliflozin induced apoptosis via the downregulation of cFLIPL and an increase in cFLIPS instability, suggesting that dapagliflozin may be a feasible drug candidate for the treatment of human renal cancer.

Related Articles

Journal Cover

November-2022
Volume 24 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Jang JH, Lee T, Sung E, Song I and Kim J: Dapagliflozin induces apoptosis by downregulating cFILP<sub>L</sub> and increasing cFILP<sub>S</sub> instability in Caki‑1 cells. Oncol Lett 24: 401, 2022
APA
Jang, J.H., Lee, T., Sung, E., Song, I., & Kim, J. (2022). Dapagliflozin induces apoptosis by downregulating cFILP<sub>L</sub> and increasing cFILP<sub>S</sub> instability in Caki‑1 cells. Oncology Letters, 24, 401. https://doi.org/10.3892/ol.2022.13521
MLA
Jang, J. H., Lee, T., Sung, E., Song, I., Kim, J."Dapagliflozin induces apoptosis by downregulating cFILP<sub>L</sub> and increasing cFILP<sub>S</sub> instability in Caki‑1 cells". Oncology Letters 24.5 (2022): 401.
Chicago
Jang, J. H., Lee, T., Sung, E., Song, I., Kim, J."Dapagliflozin induces apoptosis by downregulating cFILP<sub>L</sub> and increasing cFILP<sub>S</sub> instability in Caki‑1 cells". Oncology Letters 24, no. 5 (2022): 401. https://doi.org/10.3892/ol.2022.13521