Department of Bioscience, Mokpo National University, Muan 58554, Republic of Korea.
Department of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, Republic of Korea.
Int J Med Sci. 2018 Jun 12;15(9):929-936. doi: 10.7150/ijms.26410. eCollection 2018.
Inflammation mediated by the innate immune system is an organism's protective mechanism against infectious environmental risk factors. It is also a driver of the pathogeneses of various human diseases, including cancer development and progression. Microalgae are increasingly being focused on as sources of bioactive molecules with therapeutic potential against various diseases. Furthermore, the antioxidant, anti-inflammatory, and anticancer potentials of microalgae and their secondary metabolites have been widely reported. However, the underlying mechanisms remain to be elucidated. Therefore, in this study, we investigated the molecular mechanisms underlying the anti-inflammatory and anticancer activities of the ethanol extract of the Antarctic freshwater microalga sp. (ETMI) by several assays using RAW 264.7 macrophages and HCT116 human colon cancer cells. ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. In addition, ETMI exerted cytotoxic activity against HCT116 cells in a dose-dependent manner, leading to significantly reduced cancer cell proliferation. Further, it induced cell cycle arrest in the G1 phase through the regulation of hallmark genes of the G1/S phase transition, including , and cyclin-dependent kinase 4 and 6 ( and , respectively). At the transcriptional level, the expression of gradually increased in response to ETMI treatment while that of and decreased. Taken together, our findings suggest that the anti-inflammatory and anticancer activities of the Antarctic freshwater microalga, sp., and ETMI may provide a new clue for understanding the molecular link between inflammation and cancer and that ETMI may be a potential anticancer agent for targeted therapy of colorectal cancer.
固有免疫系统介导的炎症是生物体对抗感染性环境风险因素的保护机制。它也是各种人类疾病（包括癌症发展和进展）发病机制的驱动因素。微藻作为具有治疗各种疾病潜力的生物活性分子的来源，越来越受到关注。此外，微藻及其次生代谢物的抗氧化、抗炎和抗癌潜力已被广泛报道。然而，其潜在机制仍有待阐明。因此，在这项研究中，我们通过 RAW 264.7 巨噬细胞和 HCT116 人结肠癌细胞的几种测定，研究了南极淡水微藻 sp.（ETMI）的乙醇提取物的抗炎和抗癌活性的分子机制。ETMI 通过调节主要炎症指标，如环氧化酶（COX）-2、白细胞介素（IL）-6、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子（TNF）-α 和一氧化氮（NO），发挥其抗炎活性，呈剂量依赖性。此外，ETMI 以剂量依赖性方式对 HCT116 细胞发挥细胞毒性作用，导致癌细胞增殖显著减少。此外，它通过调节 G1/S 期转换的标志性基因，如 、 和细胞周期蛋白依赖性激酶 4 和 6（和 ，分别），诱导细胞周期停滞在 G1 期。在转录水平上，随着 ETMI 处理，的表达逐渐增加，而 和 的表达减少。总之，我们的研究结果表明，南极淡水微藻 sp.和 ETMI 的抗炎和抗癌活性可能为理解炎症和癌症之间的分子联系提供新的线索，并且 ETMI 可能是结直肠癌靶向治疗的潜在抗癌药物。
