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铑(II)配合物与 2-苯甲酰吡啶,一种新型的潜在化疗药物,诱导 HepG2 细胞周期停滞和细胞凋亡。

Rhodium (II) complex with 2-benzoylpyridine, a novel potential chemotherapeutic drug, induces cell cycle arrest and apoptosis in HepG2 cells.

机构信息

Department of Pathology, the Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, China.

Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, 15 Lequn Road, Guilin, 541001, Guangxi, China.

出版信息

Biometals. 2017 Dec;30(6):903-915. doi: 10.1007/s10534-017-0056-4. Epub 2017 Oct 9.

Abstract

Rhodium (II) complex with 2-benzoylpyridine (Rh(L)Cl) is a new, synthetic, active metal-complex, which is produced by the reaction of 2-benzoylpyridine (L) with rhodium chloride hydrate (RhCl·nHO). The crystal structure was determined by X-ray diffraction which is mono-nuclear. In order to explore the biological properties of the novel complex, a series of studies were performed. The results showed that Rh(L)Cl had the anti-tumor activity in HepG and other cell lines and has been shown to induce G1 cell cycle arrest and apoptosis in HepG cells. The anti-cancer effect of Rh(L)Cl is regulated by increased expression of caspase-3 and PARP via the mitochondrial and the death receptor pathways. Bcl-2 family proteins might play an important role in the Rh(L)Cl-induced changes in these two pathways. Further studies indicated that Rh(L)Cl increased the level of reactive oxygen species (ROS), but that Rh(L)Cl-induced apoptosis was ROS-independent. In conclusion, Rh(L)Cl is a potential new anti-tumor drug, which induces HepG cell death via the mitochondrial and death receptor pathways and has no obvious toxicity to normal liver cell.

摘要

铑(II)配合物与 2-苯甲酰吡啶(Rh(L)Cl)是一种新型的合成活性金属配合物,它是由 2-苯甲酰吡啶(L)与水合氯化铑(RhCl·nHO)反应生成的。通过 X 射线衍射确定了其晶体结构,为单核结构。为了探索新型配合物的生物学特性,进行了一系列研究。结果表明,Rh(L)Cl 在 HepG 和其他细胞系中具有抗肿瘤活性,并已被证明可诱导 HepG 细胞的 G1 细胞周期停滞和凋亡。Rh(L)Cl 的抗癌作用通过增加 caspase-3 和 PARP 的表达通过线粒体和死亡受体途径进行调节。Bcl-2 家族蛋白可能在这两条途径的 Rh(L)Cl 诱导变化中起重要作用。进一步的研究表明,Rh(L)Cl 增加了活性氧物种(ROS)的水平,但 Rh(L)Cl 诱导的凋亡与 ROS 无关。总之,Rh(L)Cl 是一种有潜力的新型抗肿瘤药物,通过线粒体和死亡受体途径诱导 HepG 细胞死亡,对正常肝细胞无明显毒性。

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