Cancer cell-specific anticancer effects of Coptis chinensis on gefitinib-resistant lung cancer cells are mediated through the suppression of Mcl-1 and Bcl-2

Jae Hwan Kim, Eun Sun Ko, Dasom Kim, Seong Hee Park, Eun Jung Kim, Jinkyung Rho, Hyemin Seo, Min Jung Kim, Woong Mo Yang, In Jin Ha, Myung Jin Park, Ji Yun Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR-TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance. In the present study, the anticancer potential of natural extracts of Coptis chinensis (ECC) against gefitinib-resistant (GR) NSCLC cells were investigated in vitro and in vivo. ECC inhibited the viability, migration and invasion, and effectively induced the apoptosis of GR cells. These effects were associated with the suppression of EGFR/AKT signaling and the expression of anti-apoptotic proteins, Mcl-1 and Bcl-2, which were overexpressed in GR NSCLC cells. Combination treatment with ECC and gefitinib enhanced the sensitivity of GR cells to gefitinib in vitro, but not in vivo. However, ECC increased the survival of individual zebrafish without affecting the anticancer effect to cancer cells in vivo, which indicated a specific cytotoxic effect of ECC on cancer cells, but not on normal cells; this is an important property for the development of novel anticancer drugs. On the whole, the findings of the present study indicate the potential of ECC for use in the treatment of NSCLC, particularly in combination with EGFR-TKI therapy, in EGFR-TKI-resistant cancers.

Original languageEnglish
Pages (from-to)1540-1550
Number of pages11
JournalInternational journal of oncology
Volume56
Issue number6
DOIs
Publication statusPublished - 2020

Keywords

  • Apoptosis
  • Coptis chinensis
  • Epidermal growth factor receptor
  • Epidermal growth factor receptor-tyrosine kinase inhibitor resistance
  • Gefitinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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