In vitro and in vivo anti-tumour effects of MPT0B014, a novel derivative aroylquinoline, and in combination with erlotinib in human non-small-cell lung cancer cells

An Chi Tsai, Hui Chen Pai, Chih Ya Wang, Jing Ping Liou, Che Ming Teng, Jing Chi Wang, Shiow Lin Pan

Research output: Contribution to journalArticle

4 Citations (Scopus)


Background and Purpose The purpose of the current study was to assess a novel anti-cancer drug, MPT0B014, which is not a substrate for the P-glycoprotein (P-gp) transporter, alone and in combination with erlotinib, against human non-small cell lung cancer (NSCLC). Experimental Approach Cytotoxicity in human NSCLC cell lines was assessed by sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Cell cycle phase distributions were estimated with FACScan flow cytometry. Protein expression was detected by Western blotting analysis. Efflux of rhodamine 123 or calcein-acetoxymethylester was used to study the P-gp profile. The A549 xenograft model in mice was used to assess in vivo anti-tumour activity. Key Results MPT0B014 showed potent anti-proliferative activity against A549, H1299 and H226 cells. It induced G2/M arrest with down-regulation of Cdc (Tyr15) and Cdc25C, and up-regulation of cyclin B1, phospho-Cdc2 (Thr161) and Aurora A/B. P-gp-overexpressing National Cancer Institute/Adriamycin-Resistant cells were also sensitive to B014. B014-induced loss of Mcl-1 was accompanied by activation of caspases-3, -7, -8 and -9, and initiation of apoptosis. B014 in combination with erlotinib caused significant tumour inhibition in vitro and in vivo. Conclusions and Implications MPT0B014 exerted cytotoxicity against human NSCLC cell lines with little susceptibility to P-gp. Combined with the EGF receptor inhibitor, erlotinib, MPT0B014 exerted significant growth inhibition of A549 cells both in vitro and in vivo. B014 could be useful as an anti-cancer agent.

Original languageEnglish
Pages (from-to)122-133
Number of pages12
JournalBritish Journal of Pharmacology
Issue number1
Publication statusPublished - Jan 2014



  • apoptosis
  • Mcl-1
  • mitosis arrest
  • MPT0B014
  • P-gp

ASJC Scopus subject areas

  • Pharmacology

Cite this