Dibenzolium induces apoptosis and inhibits epithelial-mesenchymal transition (EMT) in bladder cancer cell lines
Yura Jotatsu1, Jack L Arbiser2, Michika Moriwaki1
1Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Sumaku, Kobe, 654-0142, Japan.
Abstract:
Bladder cancer treatments are highly aggressive and have strong side effects. Safer and more effective treatments are needed. In this study, Dibenzolium (DIB), a potent NADPH oxidase inhibitor, was evaluated for its anti-tumor effects. KK-47 (non-invasive), T24 and 5637 (invasive) cells were used in experiments. Cell proliferation, apoptosis and wound healing assays and western blotting were conducted. In addition, DIB was intratumorally administered to mice bearing KK-47, T24 and 5637 tumors, and tumor size and weight were observed over time. After removing tumors, immunohistochemistry (IHC) staining was conducted. Cell proliferation was significantly suppressed in all cell lines, and apoptotic cells increased in the KK-47 and T24 cell lines after DIB. Wound healing was suppressed in all cell lines by DIB. In KK-47 and T24, DIB increased the protein expression of the epithelial marker E-cadherin. In vivo, DIB safely suppressed tumor growth in all cell lines-bearing mice. Cleaved-Caspase-3 and E-cadherin expression increased in KK-47 and T24 tumors after DIB. In conclusion, DIB inhibited tumor growth by inducing apoptosis through the Caspase-3 pathway and reduced migration and invasion by suppressing epithelial mesenchymal transition (EMT) in bladder cancer similarly shown as our previous study of prostate cancer.
Insights
Dibenzolium (DIB), an NADPH oxidase inhibitor, effectively suppressed bladder cancer growth by inducing apoptosis and reducing cell migration. This novel therapeutic approach shows promise for safer and more effective bladder cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Bladder cancer treatments are aggressive with severe side effects.
- There is a critical need for safer, more effective bladder cancer therapies.
- NADPH oxidase inhibitors represent a potential therapeutic avenue.
Purpose of the Study:
- To evaluate the anti-tumor effects of Dibenzolium (DIB), a NADPH oxidase inhibitor, on bladder cancer.
- To investigate DIB's impact on cancer cell proliferation, apoptosis, and migration.
- To assess DIB's efficacy and safety in preclinical mouse models of bladder cancer.
Main Methods:
- In vitro: Assays for cell proliferation, apoptosis, and wound healing on KK-47, T24, and 5637 bladder cancer cell lines.
- Western blotting to analyze protein expression (e.g., E-cadherin, Caspase-3).
- In vivo: Intratumoral administration of DIB in mice bearing bladder tumors, followed by tumor measurement and immunohistochemistry.
Main Results:
- DIB significantly suppressed proliferation and wound healing in all tested bladder cancer cell lines.
- DIB induced apoptosis in KK-47 and T24 cells and increased E-cadherin expression.
- In vivo, DIB safely inhibited tumor growth and upregulated cleaved-Caspase-3 and E-cadherin in tumors.
Conclusions:
- Dibenzolium demonstrates significant anti-tumor activity in bladder cancer models.
- DIB inhibits tumor growth via apoptosis induction (Caspase-3 pathway) and reduced cell migration.
- DIB suppresses epithelial-mesenchymal transition (EMT), offering a promising therapeutic strategy for bladder cancer.
