Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran.
Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Biomed Res Int. 2021 Nov 16;2021:1969863. doi: 10.1155/2021/1969863. eCollection 2021.
Curcumin (CUR) has interesting properties to cure cancer. Cold atmospheric plasma (CAP) is also an emerging biomedical technique that has great potential for cancer treatment. Therefore, the combined effect of CAP and CUR on inducing cytotoxicity and apoptosis of melanoma cancer cells might be promising. Here, we investigated the combined effects of CAP and CUR on cytotoxicity and apoptosis in B16-F10 melanoma cancer cells compared to L929 normal cells using MTT method, acridine orange/ethidium bromide fluorescence microscopic assay, and Annexin V/PI flow cytometry. In addition, the activation of apoptosis pathways was evaluated using BCL2, BAX, and Caspase-3 (CASP3) gene expression and ratio of BAX to BCL2 (BAX/BCL2). Finally, in silico study was performed to suggest the molecular mechanism of this combination therapy on melanoma cancer. Results showed that although combination therapy with CUR and CAP has cytotoxic and apoptotic effects on cancer cells, it did not improve apoptosis rate in melanoma B16-F10 cancer cells compared to monotherapy with CAP or CUR. In addition, evaluation of gene expression in cancer cell line confirmed that CUR and CAP concomitant treatment did not enhance the expression of apoptotic genes. In silico analysis of docked model suggested that CUR blocks aquaporin- (AQP-) 1 channel and prevents penetration of CAP-induced ROS into the cells. In conclusion, combination therapy with CAP and CUR does not improve the anticancer effect of each alone.
姜黄素 (CUR) 具有治疗癌症的有趣特性。冷等离体等离子体 (CAP) 也是一种新兴的生物医学技术，在癌症治疗方面具有很大的潜力。因此，CAP 和 CUR 联合作用诱导黑色素瘤癌细胞的细胞毒性和细胞凋亡可能是有希望的。在这里，我们使用 MTT 法、吖啶橙/溴化乙锭荧光显微镜检测和 Annexin V/PI 流式细胞术，研究了 CAP 和 CUR 联合作用对 B16-F10 黑色素瘤癌细胞与 L929 正常细胞的细胞毒性和细胞凋亡的影响。此外，通过 BCL2、BAX 和 Caspase-3 (CASP3) 基因表达和 BAX/BCL2 (BAX/BCL2) 的比值评估了凋亡途径的激活。最后，进行了计算机模拟研究，以提出这种联合疗法对黑色素瘤癌症的分子机制。结果表明，尽管 CUR 和 CAP 联合治疗对癌细胞具有细胞毒性和凋亡作用，但与 CAP 或 CUR 单药治疗相比，并未提高黑色素瘤 B16-F10 癌细胞的凋亡率。此外，对癌细胞系中基因表达的评估证实，CUR 和 CAP 同时治疗并未增强凋亡基因的表达。对接模型的计算机模拟分析表明，CUR 阻断水通道蛋白- (AQP-) 1 通道，阻止 CAP 诱导的 ROS 进入细胞。总之，CAP 和 CUR 的联合治疗并没有提高每种药物单独治疗的抗癌效果。
