Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand.
Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; Department of Integrated Science, Forensic Science Program, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand.
Environ Toxicol Pharmacol. 2018 Sep;62:164-176. doi: 10.1016/j.etap.2018.07.007. Epub 2018 Jul 19.
Conventional colon cancer treatments have been associated with side effects. Consequently, the discovery of novel effective and safe therapies is urgently needed. Hence, cationic antimicrobial peptides KT2 and RT2 were evaluated towards human colon cancer HCT-116 cells. The MTT assay indicated that both KT2 and RT2 exhibited anticancer activity with good therapeutic indices, and were found to be non-toxic to non-cancerous Vero cells. The IC values of KT2 were determined as 111.96 and 90.25 μg/mL while RT2 showed IC as 104.07 and 87.84 μg/mL after 12 and 24 h treatments, respectively. Moreover, KT2 and RT2 treatment caused a significant reduction in PI3K, AKT1 and mTOR mRNA expression levels, which resulted in suppression either of HCT-116 proliferation or migration. The mechanism involved in apoptosis induction were due to decreased Bcl-2 and XIAP and increased p53, cytochrome c, caspase-2, caspase-3, caspase-8, and caspase-9 mRNA expression levels. These effects increased the level of cell cycle associated gene p21 and decreased cyclin B1 and cyclin D1 expression.
传统的结肠癌治疗方法存在副作用。因此，迫切需要发现新型有效且安全的治疗方法。因此，评估了阳离子抗菌肽 KT2 和 RT2 对人结肠癌细胞 HCT-116 的作用。MTT 法表明，KT2 和 RT2 均表现出抗癌活性，治疗指数良好，且对非癌细胞 Vero 无毒性。KT2 的 IC 值分别为 111.96 和 90.25μg/mL，而 RT2 在 12 和 24 h 处理后分别显示出 IC 为 104.07 和 87.84μg/mL。此外，KT2 和 RT2 处理导致 PI3K、AKT1 和 mTOR mRNA 表达水平显著降低，从而抑制 HCT-116 的增殖或迁移。诱导细胞凋亡的机制是由于 Bcl-2 和 XIAP 减少，p53、细胞色素 c、caspase-2、caspase-3、caspase-8 和 caspase-9 mRNA 表达水平增加。这些作用增加了细胞周期相关基因 p21 的水平，并降低了细胞周期蛋白 B1 和细胞周期蛋白 D1 的表达。
