Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90 Cumaratunga Munidasa Mawatha, Colombo, Sri Lanka.
Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu, Nepal.
Biomed Res Int. 2018 Jul 24;2018:3171348. doi: 10.1155/2018/3171348. eCollection 2018.
Current breast cancer therapies have limitations in terms of increased drug resistance resulting in short-term efficacy, thus demanding the discovery of new therapeutic agents. In this study, cytotoxic activity and apoptotic effects of govaniadine isolated from Wall. roots were determined on human breast cancer (MCF-7) cells. The SRB assay result revealed that govaniadine led to dose- and time-dependent cytotoxic effect in MCF-7 cells along with less cytotoxicity against MCF-10A cells. Govaniadine-induced apoptosis was also accompanied by upregulation of , , and mRNA expression as assessed by real time PCR analysis. Flow cytometric analysis with Annexin V and PI staining indicated that govaniadine is a potent inducer of apoptosis in MCF-7 cell lines. Distinctive morphological changes contributed to apoptosis and DNA laddering were observed in govaniadine-treated MCF-7 cells. Caspase-7 was significantly activated in treated MCF-7 cells. Govaniadine-treated MCF-7 cells also showed enhanced levels of intracellular reactive oxygen species (ROS) and glutathione S-transferase (GST) and decreased levels of glutathione (GSH). The results indicate that govaniadine has potent and selective cytotoxic effects against MCF-7 cells and the potential to induce caspase 7 dependent apoptosis in MCF-7 cells by activation of pathways that lead to oxidative stress.
目前的乳腺癌治疗方法在增加药物耐药性方面存在局限性，导致短期疗效不佳，因此需要发现新的治疗药物。在这项研究中，从 Wall. 根部分离得到的 govaniadine 的细胞毒性活性和凋亡作用在人乳腺癌（MCF-7）细胞上进行了测定。SRB 测定结果表明，govaniadine 导致 MCF-7 细胞中呈剂量和时间依赖性的细胞毒性作用，同时对 MCF-10A 细胞的细胞毒性较小。通过实时 PCR 分析评估，govaniadine 诱导的细胞凋亡还伴随着 、 和 mRNA 表达的上调。用 Annexin V 和 PI 染色的流式细胞术分析表明，govaniadine 是 MCF-7 细胞系中凋亡的有效诱导剂。在 govaniadine 处理的 MCF-7 细胞中观察到独特的形态变化，有助于凋亡和 DNA 梯状。在经处理的 MCF-7 细胞中，caspase-7 明显被激活。在经 govaniadine 处理的 MCF-7 细胞中，细胞内活性氧（ROS）和谷胱甘肽 S-转移酶（GST）水平升高，谷胱甘肽（GSH）水平降低。结果表明，govaniadine 对 MCF-7 细胞具有强大而选择性的细胞毒性作用，并通过激活导致氧化应激的途径，具有诱导 caspase 7 依赖性 MCF-7 细胞凋亡的潜力。
