Targeting mitophagy using isoliensinine as a therapeutic strategy for renal cell carcinoma treatment

Abstract

Renal cell carcinoma (RCC) is a formidable and lethal form of kidney cancer, necessitating the exploration of novel therapeutic options. Isoliensinine, an alkaloid derived from lotus seed embryos, has shown promising anti-cancer properties. However, its mechanistic actions and impact on mitochondrial dynamics remain poorly understood. This research has aimed to investigate the effects of isoliensinine on RCC, as well as its potential involvement in mitophagy and mitochondrial function. In vitro experiments utilizing RCC cell lines (786-O and ACHN) have demonstrated that isoliensinine treatment significantly reduced cell viability. Moreover, isoliensinine induced an increase in cellular and mitochondrial reactive oxygen species (ROS) levels, accompanied by reduced mitochondria membrane potential, indicating an influence on mitochondrial function. Furthermore, MitoTracker staining revealed distinct mitochondrial morphologies, with isoliensinine promoting mitochondrial fission, thus supporting its role in mitochondrial dynamics. Notably, isoliensinine led to a time-dependent upregulation of mitophagy-related proteins, indicative of mitophagy activation. Of particular interest, the addition of MitoTEMPO, a potent mitochondrial ROS scavenger, effectively reversed the isoliensinine-induced upregulation of mitophagy-related protein expression and mitochondrial ROS levels. These combined results provide novel insight into the impact of isoliensinine-induced mitophagy on mitochondrial dynamics in renal carcinoma cells. Overall, the findings from this study highlight isoliensinine as a promising candidate with significant potential for further investigation and eventual clinical application in RCC therapy. Moreover, the modulation of mitochondrial dynamics, mitophagy and ROS levels through the use of isoliensinine further adds to its appeal as a potential therapeutic agent.