Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
Department of Biotechnology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2020 Oct 26;21(21):7947. doi: 10.3390/ijms21217947.
We recently isolated a cardiac glycoside (CG), αldiginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays). Here, we report that αldiginoside caused Sphase arrest and apoptosis, through the inhibition of a series of signaling pathways, including those mediated by cyclin E, phospho-CDC25C (p-CDC25C), and janus kinase/signal transducer and activator of transcription (JAK/STAT)3. αldiginoside induced apoptosis, as indicated by caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. Equally important, αldiginoside reduced Mcl-1 expression through protein degradation, and overexpression of Mcl-1 partially protected SCC2095 cells from αldiginoside's cytotoxicity. Taken together, these data suggest the translational potential of αldiginoside to foster new therapeutic strategies for OSCC treatment.
我们最近从台湾的一种本土植物中分离得到一种强心苷（CG），αldiginoside，它在口腔鳞状细胞癌（OSCC）细胞系（SCC2095 和 SCC4，IC <0.2 μM；3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）测定）中表现出很强的肿瘤抑制作用。在这里，我们报告说，αldiginoside 通过抑制一系列信号通路，包括细胞周期蛋白 E、磷酸化 CDC25C（p-CDC25C）和 Janus 激酶/信号转导和转录激活因子（JAK/STAT）3，导致 S 期阻滞和细胞凋亡。αldiginoside 通过半胱天冬酶激活和聚（ADP-核糖）聚合酶（PARP）裂解诱导细胞凋亡。同样重要的是，αldiginoside 通过蛋白降解降低 Mcl-1 的表达，而过表达 Mcl-1 可部分保护 SCC2095 细胞免受 αldiginoside 的细胞毒性。总之，这些数据表明αldiginoside 具有转化潜力，可以为 OSCC 的治疗提供新的治疗策略。
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