Zhang Ting, Wang Ting, Cai Peiling
Department of Medical Cell Biology and Genetics, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Department of Anatomy and Histology, School of Medicine, Chengdu University, Chengdu, Sichuan 610106, P.R. China.
Mol Med Rep. 2017 Jun;15(6):3566-3574. doi: 10.3892/mmr.2017.6480. Epub 2017 Apr 13.
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‑immunoprecipitation 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.
长期以来,人们一直报道了香紫苏醇的抗癌作用,然而,香紫苏醇在宫颈癌中的抗肿瘤作用的确切机制仍有待充分阐明。本研究通过MTT和FITC-Annexin V检测分析细胞增殖和细胞凋亡。通过蛋白质印迹法测定小窝蛋白-1(Cav-1)和铜锌超氧化物歧化酶(SOD)1的蛋白水平,并通过免疫共沉淀实验研究Cav1和热休克蛋白70(HSC70)的相互作用。本研究发现,香紫苏醇抑制HeLa细胞的增殖并诱导其凋亡。两种与癌症相关的蛋白Cav1和SOD1被确定为香紫苏醇在HeLa细胞中的潜在靶点。用香紫苏醇处理细胞时,Cav1的表达增加,且SOD1的蛋白水平与Cav1呈负相关。Cav1的过表达增强了HeLa细胞对香紫苏醇处理的敏感性,并下调了SOD1的蛋白水平,这表明Cav1和SOD1之间存在潜在关联。此外,香紫苏醇通过靶向Cav1和SOD1,显著增强了几种癌细胞对硼替佐米抗癌作用的敏感性。综上所述,本研究结果表明,香紫苏醇通过上调Cav1抑制肿瘤细胞生长,并为人类癌症提供了一个潜在的治疗靶点。