Effects of betulinic acid on AKT/mTOR pathway in renal cell carcinoma

Objective: Renal cancer is the most lethal among urological cancer. Treatments of renal cell carcinoma (RCC) may be possible by immune checkpoint inhibitors and drug treatment targeting different molecules. We aimed to determine the apoptotic effect of betulinic acid and its effects on expressions of apoptosis-associated genes AKT-1 and mTOR in RCC cells. Material and methods: In this study, we investigated the apoptotic activity of betulinic acid in CAKI-2 cellline and its effect on AKT-1 and mTOR gene expression levels. In order to do so, following analyses wereconducted: WST-1 to identify the toxic effect of betulinic acid, Caspase-3/BCA to detect caspase enzyme activity, Annexin-V and ELISA to determine for apoptotic effect, and finally, real-time PCR for expression levels of AKT-1 and mTOR. Results: Our study showed that different concentrations of betulinic acid induced apoptosis in renal cancer; however, no effect was observed in healthy cells. In gene expression analysis, there was statistically significant decrease in AKT-1 expression level while increasing mTOR expression level. Conclusion: We suggested that betulinic acid with its apoptotic effect on RCC line and nontoxic effect on healthy cell line and the effects on AKT/mTOR pathway may be a potential anticancer drug promising for future studies.

Automated summary

This study demonstrates the apoptotic effect of betulinic acid on renal cancer cells and its non-toxic effect on healthy cells. Gene expression analysis reveals a significant decrease in AKT-1 expression level and an increase in mTOR expression level. Therefore, betulinic acid may be a potential anticancer drug worthy of further investigation.