Abstract
Resveratrol, known as phytoalexin, is a natural compound. Clinical studies have revealed that resveratrol has a variety of effects including anti‑inflammatory, antivirus and tumor suppressor activities. It has been reported that it may serve an important role in renal cell carcinoma (RCC) however, the molecular mechanism underlying resveratrol‑induced apoptosis in RCC is still unclear. The aim of the present study was to determine whether resveratrol could suppress RCC progression. Analysis of apoptosis demonstrated that resveratrol may act as a RCC suppressor in a dose‑ and time‑dependent manner. In addition, the results of the MTT and cell migration experiments revealed that resveratrol significantly decreased cell viability and migration. In addition, the expression of the anti‑apoptosis gene B‑cell lymphoma 2 (Bcl‑2) was downregulated by resveratrol, and the expression of pro‑apoptosis gene Bcl‑2‑associated X was upregulated at the mRNA and protein levels. Resveratrol also promoted the expression of p53 and activated phospho‑AMP‑activated protein kinase (AMPK). The phosphorylation of mammalian target of rapamycin (mTOR) was inhibited and the autophagy‑associated genes, light chain 3, autophagy related (ATG)5 and ATG7, were upregulated at the mRNA and protein levels. In conclusion, resveratrol suppressed RCC viability and migration, and promoted RCC apoptosis via the p53/AMPK/mTOR‑induced autophagy signaling pathway.
Highlights
Renal cell carcinoma (RCC), a complex metabolic disease that is associated with a number of different types of cancer, Key words: resveratrol, renal cell carcinoma cell, p53, AMP‐activated protein kinase, mammalian target of rapamycin, autophagy occurs in the kidney
The current principle of targeted RCC therapy is based on the known molecular mechanisms of renal cancer and aims to prevent the proliferation of tumor cells and inhibit angiogenesis; Von Hippel‐Lindau tumor suppressor and mammalian target of rapamycin (mTOR) [3] are the widely used targets in clinical practice. p53, a tumor suppressor protein, serves an important role in apoptosis and the inhibition of angiogenesis; it is essential for mouse double minute 2 proto‐oncogene antagonist induced RCC cell apoptosis [4]
When compared with the normal kidney HK‐2 cells, the expression of p53 was significantly decreased in Ketr‐3 cells (Fig. 5). These results indicated that p53 may serve an important role in resveratrol‐induced Ketr‐3 cell apoptosis
Summary
Renal cell carcinoma (RCC), a complex metabolic disease that is associated with a number of different types of cancer, Key words: resveratrol, renal cell carcinoma cell, p53, AMP‐activated protein kinase, mammalian target of rapamycin, autophagy occurs in the kidney. The current principle of targeted RCC therapy is based on the known molecular mechanisms of renal cancer and aims to prevent the proliferation of tumor cells and inhibit angiogenesis; Von Hippel‐Lindau tumor suppressor and mTOR [3] are the widely used targets in clinical practice. P53, a tumor suppressor protein, serves an important role in apoptosis and the inhibition of angiogenesis; it is essential for mouse double minute 2 proto‐oncogene antagonist induced RCC cell apoptosis [4]. A previous study demonstrated that co‐treatment with curcumin and temsirolimus activated the expression of p53, which induced RCC cell apoptosis [5]. P53 crosslinking with transglutaminase 2 led to p53 depletion and tumor survival [6]; these findings suggested that p53 may be a key regulator in RCC
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