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
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism*
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Animals
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Artemisinins / pharmacology*
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Artesunate
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Death / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Lung Neoplasms / enzymology
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Lung Neoplasms / genetics*
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Lung Neoplasms / pathology
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Male
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Mice
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Mice, Inbred BALB C
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Xenograft Model Antitumor Assays*
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Artemisinins
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Neoplasm Proteins
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RNA, Messenger
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Artesunate
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EGFR protein, human
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ErbB Receptors
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Proto-Oncogene Proteins c-akt