Department of Biotechnology, University of Calicut, Malappuram, 673635, Kerala, India.
Molecular Structure Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sci Rep. 2021 Jan 12;11(1):552. doi: 10.1038/s41598-020-79414-8.
Zingiberaceae plants are well known for their use in ethnomedicine. Curcuma mutabilis Škorničk., M. Sabu & Prasanthk., is an endemic Zingiberaceae species from Western Ghats of Kerala, India. Here, we report for the first time, the anticancer potential of petroleum ether extract from C. mutabilis rhizome (CMRP) and a novel labdane diterpenoid, (E)-14, 15-epoxylabda-8(17), 12-dien-16-al (Cm epoxide) isolated from it. CMRP was found to be a mixture of potent bioactive compounds including Cm epoxide. Both the extract and the compound displayed superior antiproliferative activity against several human cancer cell lines, without any display of cytotoxicity towards normal human cells such as peripheral blood derived lymphocytes and erythrocytes. CMRP treatment resulted in phosphatidylserine externalization, increase in the levels of intracellular ROS, Ca, loss of mitochondrial membrane potential as well as fragmentation of genomic DNA. Analyses of transcript profiling and immunostained western blots of extract-treated cancer cells confirmed induction of apoptosis by both intrinsic and extrinsic pathways. The purified compound, Cm epoxide, was also found to induce apoptosis in many human cancer cell types tested. Both CMRP and the Cm epoxide were found to be pharmacologically safe in terms of acute toxicity assessment using Swiss albino mice model. Further, molecular docking interactions of Cm epoxide with selected proteins involved in cell survival and death were also indicative of its druggability. Overall, our findings reveal that the endemic C. mutabilis rhizome extract and the compound Cm epoxide isolated from it are potential candidates for development of future cancer chemotherapeutics.
姜科植物因其在民族医学中的应用而闻名。姜黄属植物 Curcuma mutabilis Škorničk.、M. Sabu & Prasanthk. 是印度喀拉拉邦西高止山脉的特有姜科植物。在这里，我们首次报道了来自 C. mutabilis 根茎的石油醚提取物（CMRP）和一种新型的贝壳杉烷二萜，（E）-14,15-环氧贝壳杉烷-8(17),12-二烯-16-醛（Cm 环氧）的抗癌潜力。CMRP 被发现是一种包含 Cm 环氧在内的有效生物活性化合物的混合物。提取物和化合物均对多种人类癌细胞系表现出卓越的抗增殖活性，而对正常人类细胞（如外周血衍生的淋巴细胞和红细胞）没有任何细胞毒性。CMRP 处理导致磷脂酰丝氨酸外翻、细胞内 ROS、Ca 水平升高、线粒体膜电位丧失以及基因组 DNA 片段化。对提取物处理的癌细胞的转录谱分析和免疫染色 Western blot 分析证实了两种内在和外在途径诱导的细胞凋亡。纯化的化合物 Cm 环氧也被发现能诱导许多测试的人类癌细胞类型的凋亡。CMRP 和 Cm 环氧在使用瑞士白化病小鼠模型进行的急性毒性评估中均被发现具有药理安全性。此外，Cm 环氧与参与细胞存活和死亡的选定蛋白的分子对接相互作用也表明了其成药性。总的来说，我们的研究结果表明，特有种姜黄属植物的根茎提取物和从其中分离出的化合物 Cm 环氧可能是未来癌症化疗药物的候选物。
