Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan.
Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan.
Int J Mol Sci. 2017 Jul 13;18(7):1508. doi: 10.3390/ijms18071508.
Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.
黑色素瘤是最恶性的皮肤癌，预后非常差。本研究旨在评估川陈皮素 C 对 A375.S2 黑色素瘤细胞的凋亡作用，并确定凋亡相关的潜在机制。通过 MTT 和实时细胞毒性测定来确定细胞活力。用 Annexin V-FITC 和碘化丙啶对细胞进行染色后，通过流式细胞术评估细胞凋亡。使用 JC-1 测定评估线粒体膜电位。使用 CellROX 测定来测量细胞内 ROS 的产生，而使用 MitoSOX 测定来评估线粒体 ROS 的产生。结果表明，川陈皮素 C 抑制 A375.S2 黑色素瘤细胞的生长，并通过增加线粒体 ROS 产生介导的线粒体途径促进细胞凋亡。此外，川陈皮素 C 诱导 A375.S2 细胞中 MAPKs（p38、ERK 和 JNK）的磷酸化，并上调凋亡蛋白（Puma、Bax、Bad、Bid、Apaf-1、细胞色素 C、caspase-9 和 caspase-3/7）的表达。用 MitoTEMPOL（一种线粒体靶向抗氧化剂）预处理 A375.S2 细胞可减弱 MAPKs 的磷酸化、凋亡蛋白的表达以及细胞凋亡的整体进展。总之，川陈皮素 C 通过增加线粒体 ROS 的产生诱导 A375.S2 黑色素瘤细胞凋亡，从而激活 p38、ERK 和 JNK，并增加凋亡蛋白的表达。因此，川陈皮素 C 可能被视为治疗恶性黑色素瘤的一种潜在形式。
Naunyn Schmiedebergs Arch Pharmacol. 2024-2
Signal Transduct Target Ther. 2022-8-13
Int J Mol Sci. 2021-7-12
Semin Cancer Biol. 2016-10
Evid Based Complement Alternat Med. 2015
Zotero 插件
