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

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Abstract

Rhodium (II) complex with 2-benzoylpyridine (Rh(L)2Cl2) is a new, synthetic, active metal-complex, which is produced by the reaction of 2-benzoylpyridine (L) with rhodium chloride hydrate (RhCl3·nH2O). 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)2Cl2 had the anti-tumor activity in HepG2 and other cell lines and has been shown to induce G1 cell cycle arrest and apoptosis in HepG2 cells. The anti-cancer effect of Rh(L)2Cl2 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)2Cl2-induced changes in these two pathways. Further studies indicated that Rh(L)2Cl2 increased the level of reactive oxygen species (ROS), but that Rh(L)2Cl2-induced apoptosis was ROS-independent. In conclusion, Rh(L)2Cl2 is a potential new anti-tumor drug, which induces HepG2 cell death via the mitochondrial and death receptor pathways and has no obvious toxicity to normal liver cell.

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Abbreviations

L:

2-benzoylpyridine

NAC:

N-acetyl-L-cysteine

ROS:

Reactive oxygen species

HCC:

Hepatocellular carcinoma

ΔΨm:

Mitochondrial membrane potential

JC-1:

5, 5, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimidazolylcarbocyanine

MTT:

3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide

CDK:

Cyclin-dependent kinase

DMSO:

Dimethyl sulfoxide

NMR:

Nuclear magnetic resonance pectroscopy

MS:

Mass spectroscopy

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Acknowledgements

The present study was supported in part by the National Natural Science Foundation of China (No. 8156130230) and the Natural Science Foundation of Guangxi (2015GXNSFEA139003).

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Authors and Affiliations

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

    Xuehong Wang & Zhaoquan Huang

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

    Xuehong Wang, Yulan Li, Minglin Lin & Junfei Jin

  3. China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, 541001, Guangxi, China

    Xuehong Wang, Yulan Li, Minglin Lin & Junfei Jin

Authors
  1. Xuehong Wang
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  2. Yulan Li
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  3. Minglin Lin
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  4. Junfei Jin
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  5. Zhaoquan Huang
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Correspondence to Junfei Jin or Zhaoquan Huang.

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Electronic supplementary material

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10534_2017_56_MOESM1_ESM.docx

Supplementary information included the elemental analysis of Rh(L)2Cl2 and the IC50 Value of compounds, the IR (KBr) spectra, the 1HNMR (600 MHz, DMSO-d6) of Rh(L)2Cl2, the cell cycle of HepG2 treated with Rh(L)2Cl2 and L. Supplementary material 1 (DOCX 200 kb)

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Wang, X., Li, Y., Lin, M. et al. Rhodium (II) complex with 2-benzoylpyridine, a novel potential chemotherapeutic drug, induces cell cycle arrest and apoptosis in HepG2 cells. Biometals 30, 903–915 (2017). https://doi.org/10.1007/s10534-017-0056-4

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  • DOI: https://doi.org/10.1007/s10534-017-0056-4

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