Curcumin induces apoptosis and autophagy inhuman renal cell carcinoma cells via Akt/mTOR suppression
Xuelian Gong, Ling Jiang, Wei Li, Qingbin Liang, Zhen Li
Abstract
Renal cell carcinoma (RCC) is a highly aggressive cancer leading to high economic and social burden, and has increasing annual cases. Curcumin is a traditional Chinese medicine widely used as anti-inflammatory, anti-viral and anti-cancer agent, thus can be applicable in RCC therapy. The work assessed the effects of RCC treatment with Curcumin, Curcumin+3-MA, Curcumin+ CQ or curcumin+ Z-VAD in vitro and in vivo, and the mechanisms involved in inhibition of tumor cells proliferation. The study used ACHN tumor cells and C57BL/6 nude mice for results validation. Cell proliferation was determined through MTT assays while apoptosis was investigated using Annexin V-FITC/PI kit and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-6, IL-8, and TNF-α cytokines expressions. AKT/mTOR and autophagy proteins expressions were investigated through western blot and immunofluorescence. The results indicated significantly inhibited cell viability following ACHN tumor cells treatments with curcumin alone, or with the various combinations, as compared to the control. Apoptosis was significantly increased following curcumin treatment, but was significantly reversed after treatment with curcumin+ 3-MA. Likewise, AKT/mTOR proteins expression were significantly reduced while the autophagy-related proteins were significantly elevated following curcumin treatment. The tumor size, weight and volumes were also significantly suppressed following treatment with curcumin. In conclusion, the investigation demonstrated that curcumin suppressed ACHN cell viability, induced apoptosis and autophagy, through the suppression of AKT/mTOR pathway. Use of curcumin to target AKT/mTOR pathway could be an effective treatment alternative for renal cell carcinoma.