Cucurbitacin E induces apoptosis of human prostate cancer cells via cofilin-1 and mTORC1.

Cucurbitacin E is an important member of the cucurbitacin family and exhibits inhibitory effects in various types of cancer. Cucurbitacin is a potential antineoplastic drug; however, its anticancer effect in human prostate cancer (PC) remains unknown. The aim of the present study was to determine whether the effect of cucurbitacin E on the cell viability and apoptosis of the human PC cell line, LNCaP, was mediated by cofilin-1- and mammalian target of rapamycin (mTOR). The results of the present study demonstrated that cucurbitacin E significantly exhibited cytotoxicity, suppressed cell viability (P<0.0001) and induced apoptosis (P=0.0082) in LNCaP cells. In addition, it was demonstrated that treatment with cucurbitacin E significantly induced cofilin-1 (P=0.0031), p-mTOR (P=0.0022), AMP-activated protein kinase (AMPK; P=0.0048), cellular tumor antigen p53 (p53; P=0.0018) and caspase-9 (P=0.0026) protein expression in LNCaP cells, suggesting that cucurbitacin E exerts its effects on LNCaP cells through cofilin-1, mTOR, AMPK, p53 and caspase-9 signaling. These results suggested that cucurbitacin E maybe used as a therapeutic agent in the treatment of human PC.

miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2.

MicroRNAs play critical roles in the development and progression of human cancers. Although it has been reported that miR-106a* is downregulated in follicular lymphoma, its role in renal cell carcinoma (RCC) remains unknown. This study investigated the expression and role of miR-106a* in human RCC. Our results showed that the miR-106a* expression decreased dramatically in clinical RCC tissues and cell lines. In vitro, overexpression of miR-106a* suppressed RCC cell proliferation and S/G2 transition, whereas inhibition of miR-106a* promoted cell proliferation and S/G2 transition. It was also found that miR-106a* expression was inversely correlated with the expression of insulin receptor substrate 2 (IRS-2). IRS-2 was determined to be a direct target of miR-106a* by a luciferase reporter assay. Importantly, silencing IRS-2 resulted in the same biologic effects as those of miR-106a* overexpression in RCC cells, including inhibition of RCC cell proliferation and triggering of S/G2 cell cycle arrest with inhibition of the PI3K/Akt signaling pathway. These results indicate that miR-106a* affects RCC progression by targeting IRS-2 with suppression of the PI3K/Akt signaling pathway in RCC cells. The findings suggest miR-106a* as a novel strategy for RCC treatment.