Department of Life Science, Gachon University, Seongnam 13120, Republic of Korea.
Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Biomed Res Int. 2018 Nov 29;2018:7970618. doi: 10.1155/2018/7970618. eCollection 2018.
This study was focused on investigating the anticancer potential of indole-3-carbinol (I3C) against osteosarcoma MG-63 and U2OS cells. A wound healing assay indicated that IC3 inhibited migration of MG-63 and U2OS cells. MTT, WST-1, and colony formation assays revealed that treatment of MG-63 and U2OS cells with I3C decreased cell viability. Fluorescence-activated cell sorting (FACS) analysis showed that I3C induced apoptosis in a dose- and time-dependent manner in MG-63 and U2OS cells. Moreover, via terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP-biotin nick-end labeling (TUNEL) assay, we detected that I3C induced DNA fragmentation. Western blotting demonstrated that activated forms of caspase-3, caspase-7, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP) were increased in MG-63 and U2OS cells, following treatment with I3C. Furthermore, protein expression levels of FOXO3, Bax, and Bim extra-large form were increased while those of Akt, JNK, p38, phosphorylated ERK, and Bcl-xL were decreased by I3C treatment in MG-63 and U2OS cells. Thus, the study indicates that I3C may induce apoptosis in human osteosarcoma MG-63 and U2OS cells via the activation of apoptotic signaling pathways by FOXO3.
本研究旨在探讨吲哚-3-甲醇（I3C）对骨肉瘤 MG-63 和 U2OS 细胞的抗癌潜力。划痕愈合实验表明，I3C 抑制 MG-63 和 U2OS 细胞的迁移。MTT、WST-1 和集落形成实验表明，I3C 处理 MG-63 和 U2OS 细胞可降低细胞活力。流式细胞术（FACS）分析表明，I3C 以剂量和时间依赖的方式诱导 MG-63 和 U2OS 细胞凋亡。此外，通过末端脱氧核苷酸转移酶-（TdT-）介导的 dUTP-生物素缺口末端标记（TUNEL）实验，我们检测到 I3C 诱导 DNA 片段化。Western blot 分析表明，I3C 处理后，MG-63 和 U2OS 细胞中激活的 caspase-3、caspase-7 和 caspase-9 以及多聚（ADP-核糖）聚合酶（PARP）增加。此外，I3C 处理可增加 MG-63 和 U2OS 细胞中 FOXO3、Bax 和 Bim 特大形式的蛋白表达水平，同时降低 Akt、JNK、p38、磷酸化 ERK 和 Bcl-xL 的蛋白表达水平。因此，该研究表明，I3C 可能通过 FOXO3 激活凋亡信号通路诱导人骨肉瘤 MG-63 和 U2OS 细胞凋亡。
