Suh Sung-Suk, Kim Tai Kyoung, Kim Jung Eun, Hong Ju-Mi, Nguyen Trang Thu Thi, Han Se Jong, Youn Ui Joung, Yim Joung Han, Kim Il-Chan
Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, Korea.
Department of Pharmacy, Graduate School, Sungkyunkwan University, Suwon 16419, Korea.
Molecules. 2017 Aug 17;22(8):1361. doi: 10.3390/molecules22081361.
Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen , in the human colorectal cancer cell line HCT116. In this study, ramalin displayed concentration-dependent anticancer activity against HCT116 cells, significantly suppressing proliferation and inducing apoptosis. Furthermore, ramalin induced cell cycle arrest in the gap 2/mitosis (G2/M) phase through the modulation of hallmark genes involved in the G2/M phase transition, such as tumour protein p53 () cyclin-dependent kinase inhibitor 1A () cyclin-dependent kinase 1 () and cyclin B1 (). At both the transcriptional and translational level, ramalin caused a gradual increase in the expression of and its downstream gene , while decreasing the expression of and in a concentration-dependent manner. In addition, ramalin significantly inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that ramalin may be a therapeutic candidate for the targeted therapy of colorectal cancer.
结直肠癌是全球主要的死亡原因之一，其发生是通过多个细胞通路的高度复杂协调，从而导致癌变。最近的研究越来越多地表明，地衣提取物的成分具有强大的药学活性，包括对各种癌细胞的抗癌活性，使其成为新型抗癌治疗药物的有希望的候选者。本研究的主要目的是评估南极地衣中的次生代谢产物拉马林在人结直肠癌细胞系HCT116中的抗癌能力。在本研究中，拉马林对HCT116细胞表现出浓度依赖性的抗癌活性，显著抑制增殖并诱导凋亡。此外，拉马林通过调节参与G2/M期转换的标志性基因，如肿瘤蛋白p53（）、细胞周期蛋白依赖性激酶抑制剂1A（）、细胞周期蛋白依赖性激酶1（）和细胞周期蛋白B1（），诱导细胞周期停滞在G2/有丝分裂（G2/M）期。在转录和翻译水平上，拉马林导致和其下游基因的表达逐渐增加，同时以浓度依赖性方式降低和的表达。此外，拉马林以浓度依赖性方式显著抑制结肠癌细胞的迁移和侵袭。综上所述，这些数据表明拉马林可能是结直肠癌靶向治疗的候选药物。
