Chrysotoxene induces apoptosis of human hepatoblastoma HepG2 cells in vitro and in vivo via activation of the mitochondria-mediated apoptotic signaling pathway

Dou,Chunqing; Han,Mingming; Zhang,Bao; Sun,Liyuan; Jin,Xin; Li,Tao

doi:10.3892/ol.2018.7857

Chrysotoxene induces apoptosis of human hepatoblastoma HepG2 cells in vitro and in vivo via activation of the mitochondria-mediated apoptotic signaling pathway

Authors:
- Chunqing Dou
- Mingming Han
- Bao Zhang
- Liyuan Sun
- Xin Jin
- Tao Li
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Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, Beijing 100048, P.R. China
Published online on: January 25, 2018 https://doi.org/10.3892/ol.2018.7857
Pages: 4611-4618

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Abstract

Previous studies have indicated that chrysotoxene may be a potential drug used to treat tumors, however the effect of chrysotoxene on hepatoblastoma remains unknown. Therefore, the present study aimed to investigate the cytotoxic effect and elucidate the potential molecular mechanism of chrysotoxene on human hepatoblastoma HepG2 cells. Chrysotoxene (5‑40 µg/ml) exhibited cytotoxic activity against HepG2 cells with inhibitory rates of 24.67‑84.06% (half maximal inhibitory concentration, 19.64 µg/ml), observed from a Cell Counting Kit‑8 assay. The results of flow cytometry analysis indicated that chrysotoxene (5, 10 or 20 µg/ml) significantly (P<0.01) induced the apoptosis of HepG2 cells with apoptotic rates of 23.14, 35.68 and 55.61% respectively, compared with the control group. The results of western blot analysis indicated that chrysotoxene (5, 10 or 20 µg/ml) significantly (P<0.05) promoted the release of second mitochondria‑derived activator of caspase (Smac) and Cytochrome c from the mitochondria to the cytoplasm, downregulated Survivin and B cell lymphoma‑2 (Bcl‑2) proteins levels, and upregulated Bcl‑2‑associated X factor (Bax), apoptotic protease activating factor‑1 (Apaf‑1), cleaved (c)‑caspase‑9 and c‑caspase‑3 protein levels in HepG2 cells, compared with the control group. The results of xenograft analysis indicated that chrysotoxene (20 mg/kg) significantly (P<0.01) inhibited the growth of HepG2 cell‑induced tumors by regulating the aforementioned apoptotic proteins (Smac, Cytochrome c, Survivin, Bcl‑2, Bax, Apaf‑1, c‑caspase‑9 and c‑caspase‑3), compared with the control group. In conclusion, chrysotoxene induced the apoptosis of HepG2 cells in vitro and in vivo via activation of the mitochondria‑mediated apoptotic signaling pathway, suggesting that it may be a potential candidate drug for treating patients with hepatoblastoma.

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