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Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells

descriptionPublicationkeyboard_double_arrow_right Article 25 Nov 2013MDPI AGInternational Journal of Molecular Sciences, volume 14, pages 23,212-23,230 (eissn: 1422-0067,

Authors: Li Wang; Chun Gao; Shu-Kun Yao; Bu-Shan Xie;

doi: 10.3390/ijms141223212

pmc: PMC3876039

pmid: 24287900

Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells

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Abstract

Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

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Subjects by Vocabulary

Library of Congress Subject Headings: lcsh:Chemistry lcsh:QH301-705.5 lcsh:Biology (General) lcsh:QD1-999

Microsoft Academic Graph classification: chemistry.chemical_compound Matrine Annexin Transfection Cell biology Biology MTT assay Protein kinase B PI3K/AKT/mTOR pathway Autophagy chemistry Apoptosis

Keywords

autophagic inhibitor, Apoptosis, chloroquine, Phosphatidylinositol 3-Kinases, matrine, Sequestosome-1 Protein, matrine; hepatocellular carcinoma; autophagy; apoptosis; autophagic inhibitor; chloroquine, RNA, Small Interfering, Matrines, Spectroscopy, Phosphoinositide-3 Kinase Inhibitors, TOR Serine-Threonine Kinases, Liver Neoplasms, hepatocellular carcinoma, Hep G2 Cells, General Medicine, Up-Regulation, Computer Science Applications, Caspases, Beclin-1, RNA Interference, Microtubule-Associated Proteins, Quinolizines, Signal Transduction, autophagy, Carcinoma, Hepatocellular, Article, Catalysis, Inorganic Chemistry, Alkaloids, Cell Line, Tumor, Humans, Physical and Theoretical Chemistry, Molecular Biology, Adaptor Proteins, Signal Transducing, Organic Chemistry, Membrane Proteins, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt

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	citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	31
	popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.	Top 10%
	influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	Average
	impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.	Top 10%

	citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	31
	popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.	Top 10%
	influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	Average
	impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.	Top 10%