Abstract 6236: Stellettin B induces apoptosis and autophagy in human bladder cancer RT112 cells

Abstract

Bladder cancer is one of the most prevalent cancers worldwide. Although most of the patients have good prognosis and good life expectancy with standard treatments, recurrence rate and five-year survival rate have not been significantly improved in patients with bladder cancer, demonstrating there is an urgent need for development of a novel therapeutic strategy for the treatment of bladder cancer. Stellettin B (SP-2), a triterpene isolated from marine sponge Jaspis stellifera , suppresses cell viability in bladder cancer RT112 cells without severe toxicity toward normal uroepithelial SV-HUC-1 cells. Our results showed that SP-2 induces accumulation of cells at subG1 phase in parallel with increase of early apoptotic cells via annexin V/PI staining and activation of cell apoptotic death proteins. Moreover, non-cytotoxic concentrations of SP-2 induces LC3-II formation and p62 downregulation to activate autophagy in RT112 cells, suggesting autophagy may play a role in SP-2 -induced cell death. Inhibition of autophagy by pharmacological inhibitors (3-MA and chloroquine) or ATG5 knockout protects stellettin B-induced apoptosis and cell viability suppression, indicating SP-2 induces autophagy to promotes cell death. Taken together, stellettin B may be a promising therapeutic agent for bladder cancer treatment. Citation Format: Mei-Chuan Chen, Chun-Han Chang. Stellettin B induces apoptosis and autophagy in human bladder cancer RT112 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6236.