Open Access

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

  • Published online on: December 8, 2017     https://doi.org/10.3892/ol.2017.7575
  • Pages:2097-2104
  • Copyright: © Zhuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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February 2018
Volume 15 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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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