Open Access

Mitochondrial pathway‑mediated apoptosis is associated with erlotinib‑induced cytotoxicity in hepatic cells

  • Authors:
    • Xueqin Chen
    • Shaoyu Yang
    • Yuelong Pan
    • Xin Li
    • Shenglin Ma
  • View Affiliations

  • Published online on: November 8, 2017     https://doi.org/10.3892/ol.2017.7359
  • Pages:783-788
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

For advanced non‑small‑cell lung cancer (NSCLC) with mutations to the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors, including erlotinib are indicated for the first‑line treatment. Liver injury is one of the multiple adverse effects of erlotinib and may affect its safety. The present study investigated the mechanism of erlotinib‑induced hepatotoxicity in vitro and provided experimental evidence for the screening of potential hepatoprotectors. Erlotinib induced dose‑dependent cytotoxicity in human L‑02 hepatic cells 72 h after treatment. In other experiments, L‑02 cells were treated with erlotinib for 48 h and thereafter exhibited typical features of apoptosis. Erlotinib caused alterations to nuclear morphology, including chromatin condensation and karyopyknosis; it also increased the fraction of late apoptotic cells and regulated apoptotic protein levels, activating caspase‑3 and cleaving of poly‑ADP‑ribose polymerase. Furthermore, 48 h exposure to erlotinib disturbed mitochondrial function by decreasing the ratio of B‑cell lymphoma 2 (Bcl‑2) to Bcl‑associated X proteins and reducing mitochondrial membrane potential. The results of this in vitro study indicate that erlotinib‑induced hepatotoxicity may occur through mitochondrial‑pathway‑mediated apoptosis.

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January 2018
Volume 15 Issue 1

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

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Chen, X., Yang, S., Pan, Y., Li, X., & Ma, S. (2018). Mitochondrial pathway‑mediated apoptosis is associated with erlotinib‑induced cytotoxicity in hepatic cells. Oncology Letters, 15, 783-788. https://doi.org/10.3892/ol.2017.7359
MLA
Chen, X., Yang, S., Pan, Y., Li, X., Ma, S."Mitochondrial pathway‑mediated apoptosis is associated with erlotinib‑induced cytotoxicity in hepatic cells". Oncology Letters 15.1 (2018): 783-788.
Chicago
Chen, X., Yang, S., Pan, Y., Li, X., Ma, S."Mitochondrial pathway‑mediated apoptosis is associated with erlotinib‑induced cytotoxicity in hepatic cells". Oncology Letters 15, no. 1 (2018): 783-788. https://doi.org/10.3892/ol.2017.7359