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IJPER · Lens · The Inhibition Effect of 2-Methoxy-1,4- naphthoquinone on Human Hepatoma Cell Lines: A in vitro and in vivo Studies

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Article · Volume 56, Issue 4 · pp. 1106–1114

The Inhibition Effect of 2-Methoxy-1,4- naphthoquinone on Human Hepatoma Cell Lines: A in vitro and in vivo Studies

Huaguo Liang1,2, Ying Wen1,2, Wei Fang1, Xiaoyan Cai1, Xiangsheng Wang1, Li Zou4, Peng Wei1, Baoyun Yang4, Jiazheng Lu4, Yongxia Yang3, Yongli Zhang1,2

  1. 1School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, PR, CHINA.
  2. 2Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou, PR, CHINA.
  3. 3School of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou, PR, CHINA.
  4. 4School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, PR, CHINA.

Abstract

Background and Aim: To study the antitumor activity of 2-Methoxy-1,4-naphthoquinone (MNQ) against hepatocellular carcinoma (HCC) cells, in an attempt to fill the knowledge gap of anti-liver cancer with MNQ.Materials and Methods: Cell viability in the presence of MNQ was assessed by MTT and effect of MNQ on HepG2 cell cycle by flow cytometry. To analyze apoptosis and its molecular mechanisms, we used a combination of Hoechst 33342 staining, annexin V binding, Rhodamine 123 staining, Real-time quantitative PCR (qPCR), western blotting and confocal microscopy. On the other hand, in vivo tumor growth was measured by a xenograft tumor nude mice model. Finally, the hematoxylin and eosin staining were used to observe the pathological changes of tumor tissue.Results: The results indicate that MNQ induced apoptosis in HCC cell lines, as demonstrated by a significant increasing of mitochondrial membrane potential and G0/G1 cell cycle arrest in HepG2 cells. Furthermore, MNQ significantly up-regulated BAD and down-regulated the expression of anti-apoptotic factors NF-κB and Bcl-2 at protein and transcription levels. Finally, in vivo studies revealed that MNQ significantly inhibited tumor growth.Conclusion: MNQ suppress the proliferation and induces apoptosis of HCC cells through mitochondrial and Rel/NF-κB signal pathways.

Keywords: 2-Methoxy-1; 4-naphthoquinone; Hepatocellular carcinoma; Apoptosis; Cell; cycle; Hematoxylin and Eosin; Antitumor mechanisms

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