Sclareol inhibits cell proliferation and sensitizes cells to the antiproliferative effect of bortezomib via upregulating the tumor suppressor caveolin-1 in cervical cancer cells

The anticancer effect of sclareol has long been reported, however, the exact mechanisms underlying the antitumorigenic effect of sclareol in cervical carcinoma remain to be fully elucidated. The present study analyzed cell proliferation and cell apoptosis by MTT and FITC-Annexin V assays. The protein levels of caveolin-1 (Cav-1) and copper-zinc superoxide dismutase (SOD) 1 were determined by western blotting, and the interaction of Cav1 and HSC70 was investigated by co-immuno-precipitation experiments. The present study found that sclareol inhibited cell proliferation and induced apoptosis in HeLa cells. Two cancer-associated proteins, Cav1 and SOD1 were identified as potential targets of sclareol in HeLa cells. The expression of Cav1 increased when the cells were treated with sclareol, and the protein level of SOD1 was negatively correlated with Cav1. The overexpression of Cav1 enhanced the sensitivity of the HeLa cells to sclareol treatment and downregulated the protein level of SOD1, which exhibited potential associations between Cav1 and SOD1. In addition, sclareol significantly sensitized several cancer cells to the anticancer effect of bortezomib by targeting Cav1 and SOD1. Taken together, the results of the present study demonstrated that sclareol inhibited tumor cell growth through the upregulation of Cav1, and provides a potential therapeutic target for human cancer.