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Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells

  • Authors:
    • Zhen‑Jian Zhuo
    • Min‑Jie Xiao
    • Hui‑Ran Lin
    • Jing Luo
    • Tao Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China, Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, P.R. China
    Copyright: © Zhuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2097-2104
    |
    Published online on: December 8, 2017
       https://doi.org/10.3892/ol.2017.7575
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Abstract

Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT inhibited the transition between G2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT may trigger Huh7 cells to undergo caspase‑dependent apoptosis as an increased proportion of cells were identified in the sub‑G1 phase, which may be a result of poly(ADP‑ribose) polymerase cleavage and caspase activation. Furthermore, 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT‑induced apoptosis was mitochondrion‑mediated. The results of the present study demonstrated that Bcl‑2‑associated X protein translocated to the mitochondria from the cytosol following 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT treatment. Notably, the phosphoinositide 3‑kinase/protein kinase B signaling pathway was involved in 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT‑treated Huh7 cells. Therefore, the results of the present study demonstrated that 3,28‑di‑(2‑nitroxy‑acetyl)‑oxy‑BT may inhibit HCC, which may be a possible application to treat HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhuo ZJ, Xiao MJ, Lin HR, Luo J and Wang T: Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells. Oncol Lett 15: 2097-2104, 2018.
APA
Zhuo, Z., Xiao, M., Lin, H., Luo, J., & Wang, T. (2018). Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells. Oncology Letters, 15, 2097-2104. https://doi.org/10.3892/ol.2017.7575
MLA
Zhuo, Z., Xiao, M., Lin, H., Luo, J., Wang, T."Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells". Oncology Letters 15.2 (2018): 2097-2104.
Chicago
Zhuo, Z., Xiao, M., Lin, H., Luo, J., Wang, T."Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells". Oncology Letters 15, no. 2 (2018): 2097-2104. https://doi.org/10.3892/ol.2017.7575
Copy and paste a formatted citation
x
Spandidos Publications style
Zhuo ZJ, Xiao MJ, Lin HR, Luo J and Wang T: Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells. Oncol Lett 15: 2097-2104, 2018.
APA
Zhuo, Z., Xiao, M., Lin, H., Luo, J., & Wang, T. (2018). Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells. Oncology Letters, 15, 2097-2104. https://doi.org/10.3892/ol.2017.7575
MLA
Zhuo, Z., Xiao, M., Lin, H., Luo, J., Wang, T."Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells". Oncology Letters 15.2 (2018): 2097-2104.
Chicago
Zhuo, Z., Xiao, M., Lin, H., Luo, J., Wang, T."Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells". Oncology Letters 15, no. 2 (2018): 2097-2104. https://doi.org/10.3892/ol.2017.7575
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