A novel nickel(II) complex of 6-methoxy-1-pyridine-β-carboline (4a) was synthesized and characterized. The cytotoxicities of the complex towards six cancer cell lines, including MGC-803, Hep G2, T24, OS-RC-2, NCI-H460, and SK-OV-3, and human normal liver cell line HL-7702 were investigated. The IC₅₀ values for MGC-803, Hep G2, T24, OS-RC-2, NCI-H460 and SK-OV-3 were generally in the micromolar range (3.77–15.10 μM), lower than those of ligand 4 and cisplatin. Furthermore, 4a (6 μM) significantly induced cell cycle arrest at the S phase, and caused the down-regulation of p-AKT, cyclin E, cyclin A and CDK2 and the up-regulation of p27. Various experiments showed that 4a induced apoptosis, activated caspase-3, increased the levels of reactive oxygen species (ROS) and enhanced the intracellular [Ca²⁺]_c levels in MGC-803. In addition, the expression of intrinsic apoptotic proteins, including cytochrome c and apaf-1, increased. Further intrinsic apoptosis was triggered via executive molecular caspase-9 and caspase-3. In short, 4a exerted its cytotoxic activity primarily through inducing cell cycle arrest at the S phase and intrinsic apoptosis.

中文翻译：

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基于 β-咔啉衍生物的镍 (ii) 络合物作为潜在的抗肿瘤剂：合成、表征和细胞毒性†‡

合成并表征了6-甲氧基-1-吡啶-β-咔啉( 4a )的新型镍( II )络合物。研究了该复合物对六种癌细胞系（包括 MGC-803、Hep G2、T24、OS-RC-2、NCI-H460 和 SK-OV-3）以及人正常肝细胞系 HL-7702 的细胞毒性。MGC-803、Hep G2、T24、OS-RC-2、NCI-H460 和 SK-OV-3 的IC ₅₀值通常在微摩尔范围内 (3.77–15.10 μM)，低于配体 4 和顺铂的 IC 50值。此外，4a (6 μM) 显着诱导细胞周期停滞在 S 期，并引起 p-AKT、细胞周期蛋白 E、细胞周期蛋白 A 和 CDK2 的下调以及 p27 的上调。各种实验表明，4a诱导细胞凋亡、激活 caspase-3、增加活性氧 (ROS) 水平并提高MGC-803 中细胞内 [Ca ²⁺ ] _c水平。此外，内在凋亡蛋白（包括细胞色素 c 和 apaf-1）的表达增加。进一步的内在细胞凋亡是通过执行分子 caspase-9 和 caspase-3触发的。简而言之，4a主要通过诱导细胞周期停滞在S期和内在凋亡来发挥其细胞毒活性。