The effects of artesunate on the expression of EGFR and ABCG2 in A549 human lung cancer cells and a xenograft model

Molecules. 2011 Dec 19;16(12):10556-69. doi: 10.3390/molecules161210556.

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Clinical and laboratory studies have suggested that multi-targeting approaches against neoplastic cells could help to increase patient survival and might reduce the emergence of cells that are resistant to single-target inhibitors. Artesunate (ART) is one of the most potent and rapidly acting antimalarial agents known, and it also exerts a profound cytotoxic activity toward cancer cells and reverses multi-drug resistance. In the present study, we found that artesunate inhibited NSCLC A549 cell growth and proliferation, induced apoptosis and suppressed tumor growth in a dose-dependent manner in A549 cells and a mouse xenograft model. Furthermore, artesunate down-regulated the expression of epidermal growth factor receptor (EGFR), Akt and ATP-binding cassette subfamily G member 2 (ABCG2) at the mRNA and protein levels in vitro and in vivo. In conclusion, artesunate is an effective anti-cancer drug that may enhance the effectiveness of other anticancer drugs and may reverse multi-drug resistance by suppressing the transcription of ABCG2, which inhibits drug efflux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Artemisinins / pharmacology*
  • Artesunate
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Xenograft Model Antitumor Assays*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Artemisinins
  • Neoplasm Proteins
  • RNA, Messenger
  • Artesunate
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt