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Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells
- Source :
- Redox Biology, Redox Biology, Vol 12, Iss, Pp 367-376 (2017)
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II). The CHE-induced expression of LC3-II was further increased in the combination treatment with chloroquine (CQ), an autophagy inhibitor, and large amounts of red-puncta were observed in the CHE-treated A549 cells with stable expression of mRFP-EGFP-LC3, indicating that CHE induces autophagy flux. Silence of beclin 1 reversed the CHE-induced expression of LC3-II. Inhibition of autophagy remarkably reversed the CHE-induced cell viability decrease and apoptosis in NCI-H1299 cells but not in A549 cells. Furthermore, CHE triggered reactive oxygen species (ROS) generation in both cell lines. A decreased level of ROS through pretreatment with N-acetyl-L-cysteine reversed the CHE-induced cell viability decrease, apoptosis, and autophagy. Taken together, CHE induced distinctive autophagy in A549 (accompanied autophagy) and NCI-H1299 (pro-death autophagy) cells and a decreased level of ROS reversed the effect of CHE in NSCLC cells in terms of cell viability, apoptosis, and autophagy.<br />Highlights • Chelerythrine induces autophagic flux in non-small cell lung cancer (NSCLC) A549 and NCI-H1299 cells. • Chelerythrine induces an accompanied autophagy in A549 cells, while a pro-death autophagy in NCI-H1299 cells. • A decreased level of ROS reverses the chelerythrine-induced apoptosis and autophagy in NSCLC cells.
- Subjects :
- 0301 basic medicine
Programmed cell death
Lung Neoplasms
Cell Survival
Clinical Biochemistry
Apoptosis
Antineoplastic Agents
Biology
NSCLC
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Autophagy
Humans
Viability assay
Chelerythrine
lcsh:QH301-705.5
Cell Proliferation
A549 cell
chemistry.chemical_classification
Benzophenanthridines
Reactive oxygen species
lcsh:R5-920
integumentary system
Dose-Response Relationship, Drug
Organic Chemistry
ROS
Cell biology
Gene Expression Regulation, Neoplastic
030104 developmental biology
chemistry
lcsh:Biology (General)
Cell culture
A549 Cells
lcsh:Medicine (General)
Reactive Oxygen Species
Microtubule-Associated Proteins
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....ce566be5172eae619ae549a4555f7dd9