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Berberine induces dose-dependent quiescence and apoptosis in A549 cancer cells by modulating cell cyclins and inflammation independent of mTOR pathway.
Berberine induces dose-dependent quiescence and apoptosis in A549 cancer cells by modulating cell cyclins and inflammation independent of mTOR pathway.
- Source :
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Life sciences [Life Sci] 2020 Mar 01; Vol. 244, pp. 117346. Date of Electronic Publication: 2020 Jan 22. - Publication Year :
- 2020
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Abstract
- Aim: Emerging studies have shown that application of low concentration of bioactive phytomolecules can confer anti-proliferative effects on tumour cells by inducing senescence pathways. The alkaloid berberine is recognized for its anti-cancer attributes but its potential to induce senescence in tumour cells is least understood.<br />Materials and Methods: The present work assessed the mechanisms pertaining to dose-dependent anti-proliferative effects of berberine in the perspective of senescence and inflammation using human non-small cell lung cancer cell line (A549).<br />Key Findings: Amongst the different tested bioactive phytomolecules, berberine treatment suppressed the proliferation of A549 cells regardless of the concentration applied. Application of low doses of berberine induced a weak SA-β-gal activity and p21 <superscript>WAF1</superscript> expression but did not show evidence of SASP activation due to absence of NF-κB activation and expression of proinflammatory genes. However, treatment with higher dose of berberine showed no evidence of SA-β-gal activity or p21 <superscript>WAF1</superscript> expression, but instead induced apoptosis and suppressed the expression of cell cyclins. The proliferative capacity of berberine treated cells was at par with control cells and no SA-β-gal activity could be observed in first generation of berberine treated cells. mTOR pathway showed no distinct activation on account of berberine treatment thereby further emphasizing that low dose of berberine induced quiescence and not senescence in A549 cells.<br />Significance: Taken together, our observations indicate that despite its strong anti-proliferative effects, low dose berberine treatment may only induce transient changes akin to quiescence that needs to be considered before implying pro-senescence attributes of berberine in cancer therapeutics.<br />Competing Interests: Declaration of competing interest No competing interest declared.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- A549 Cells
Cell Proliferation drug effects
Cyclins genetics
Humans
Inflammation metabolism
Inflammation pathology
Lung Neoplasms drug therapy
Lung Neoplasms metabolism
Signal Transduction
TOR Serine-Threonine Kinases genetics
Apoptosis drug effects
Berberine pharmacology
Cellular Senescence drug effects
Cyclins metabolism
Gene Expression Regulation, Neoplastic drug effects
Inflammation drug therapy
Lung Neoplasms pathology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 244
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31978448
- Full Text :
- https://doi.org/10.1016/j.lfs.2020.117346