Related Experiment Video
Updated: Sep 1, 2025
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Exploring the Role of Sodium-Glucose Cotransporter as a New Target for Cancer Therapy
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman, Jordan.
Purpose:
To evaluate the effects of SGLT2 inhibitors on the proliferation, tumorigenesis, migration, colony formation, apoptosis, selected gene expression pattern, and combination with known chemotherapeutic drugs in different human cancer cell lines.
Methods:
The antiproliferative and combined effects of SGLT2 inhibitors were evaluated by MTT assay. Cell migration was assessed using wound-healing and colony formation assays. Apoptosis assay was conducted using annexin V-FITC/ propidium iodide staining. SGLT2 gene expression was determined using real-time PCR.
Results:
Canagliflozin, dapagliflozin, and ipragliflozin significantly inhibited the growth of different cancer cell lines in a dose and time-dependent manner. IC50 values after 48 hours of treatment with canagliflozin, ipragliflozin, and dapagliflozin ranged from 41.97 µM to 69.49 µM, 63.67 µM to 255.80 µM, and 167.7 µM to 435.70 µM in the examined cancer cell lines, respectively. The combined treatment of SGLT2 with doxorubicin and raloxifene separately resulted in a synergistic effect in Caco-2 and A-549 cell lines. On the other hand, the combination of SGLT2 inhibitors with cisplatin resulted in an antagonistic effect in A-549, Du-145, and Panc-1 cell lines. Canagliflozin and ipragliflozin inhibited cell migration and colony formation ability at IC50 and Sub-IC50 in the examined cancer cell lines. Canagliflozin and ipragliflozin significantly induced apoptosis at IC50 and Double-IC50 in the Du-145 cell line compared to the control. Real-time PCR showed that the treatment with 0.1 IC50 and 0.2 IC50 of both canagliflozin and ipragliflozin resulted in diminished RNA expression of SGLT2, VEGF, and Bcl-2 genes in the Du-145 cell line.
Conclusion:
SGLT2 inhibitors have antiproliferation, anti-tumorigenesis, and anti-migration effects and may induce apoptosis in cancer cells. In addition, treatment with SGLT2 inhibitors resulted in the downregulation of selected genes in the Du-145 cell line.
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrate significant antiproliferative and anti-tumorigenesis effects in various cancer cell lines. These SGLT2 inhibitors also show potential in combination therapies and gene expression modulation for cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cancer remains a leading cause of mortality worldwide, necessitating novel therapeutic strategies.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors, primarily used for diabetes management, are being investigated for their potential anticancer properties.
Purpose of the Study:
- To investigate the effects of SGLT2 inhibitors on cancer cell proliferation, tumorigenesis, migration, colony formation, and apoptosis.
- To assess the gene expression patterns influenced by SGLT2 inhibitors.
- To evaluate the efficacy of SGLT2 inhibitors in combination with chemotherapeutic drugs.
Main Methods:
- MTT assay for antiproliferative and combined effects.
- Wound-healing and colony formation assays for cell migration and tumorigenesis.
- Annexin V-FITC/propidium iodide staining for apoptosis assessment.
- Real-time PCR for SGLT2 gene expression analysis.
Main Results:
- Canagliflozin, dapagliflozin, and ipragliflozin significantly inhibited cancer cell growth in a dose- and time-dependent manner.
- Synergistic effects were observed when SGLT2 inhibitors were combined with doxorubicin and raloxifene in specific cell lines, while cisplatin showed antagonistic effects.
- SGLT2 inhibitors reduced cell migration and colony formation, induced apoptosis, and downregulated SGLT2, VEGF, and Bcl-2 gene expression in cancer cells.
Conclusions:
- SGLT2 inhibitors exhibit significant antiproliferative, anti-tumorigenesis, and anti-migration properties.
- These inhibitors can induce apoptosis and modulate the expression of key genes involved in cancer progression.
- SGLT2 inhibitors hold promise as a potential therapeutic agent or adjunct therapy in oncology.
More Related Videos
Related Concept Videos
01:55Secondary Active Transport
01:26Glucose Absorption Into the Small Intestine
01:27Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:14Active Transport
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...