Open Access

ARTICLE

A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

by SHAHID KARIM^1,*, ALANOUD NAHER ALGHANMI¹, MAHA JAMAL¹, HUDA ALKREATHY¹, ALAM JAMAL², HIND A. ALKHATABI³, MOHAMMED BAZUHAIR¹, AFTAB AHMAD^4,5

1 Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2 Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
3 Department of Biochemistry, College of Science, University of Jeddah, Jeddah, 21959, Saudi Arabia
4 Health Information Technology Department, The Applied College, King Abdulaziz University, Jeddah, Saudi Arabia
5 Pharmacovigilance and Medication Safety Unit, Center of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia

* Corresponding Author: SHAHID KARIM. Email:

(This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)

Oncology Research 2024, 32(5), 817-830. https://doi.org/10.32604/or.2024.048988

Received 23 December 2023; Accepted 22 February 2024; Issue published 23 April 2024

Abstract

Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using in vitro experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as well as reductions in intracellular ATP and lactate levels. Moreover, this effect was found to be dependent on the dosages of the drugs. In addition to effectively inhibiting the cell cycle, the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression. This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications, namely CAN, DAP, and EMP, on the responsiveness to the anticancer properties of DOX. The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

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