Unknown

Dataset Information

0

Corilagin inhibits breast cancer growth via reactive oxygen species-dependent apoptosis and autophagy.


ABSTRACT: Corilagin is a component of Phyllanthus urinaria extract and has been found of possessing anti-inflammatory, anti-oxidative, and anti-tumour properties in clinic treatments. However, the underlying mechanisms in anti-cancer particularly of its induction of cell death in human breast cancer remain undefined. Our research found that corilagin-induced apoptotic and autophagic cell death depending on reactive oxygen species (ROS) in human breast cancer cell, and it occurred in human breast cancer cell (MCF-7) only comparing with normal cells. The expression of procaspase-8, procaspase-3, PARP, Bcl-2 and procaspase-9 was down-regulated while caspase-8, cleaved PARP, caspase-9 and Bax were up-regulated after corilagin treatment, indicating apoptosis mediated by extrinsic and mitochondrial pathways occurred in MCF-7 cell. Meanwhile, autophagy mediated by suppressing Akt/mTOR/p70S6K pathway was detected with an increase in autophagic vacuoles and LC3-II conversion. More significantly, inhibition of autophagy by chloroquine diphosphate salt (CQ) remarkably enhanced apoptosis, while the caspase inhibitor z-VAD-fmk failed in affecting autophagy, suggesting that corilagin-induced autophagy functioned as a survival mechanism in MCF-7 cells. In addition, corilagin induced intracellular reactive oxygen species (ROS) generation, when reduced by ROS scavenger NAC, apoptosis and autophagy were both down-regulated. Nevertheless, in SK-BR3 cell which expressed RIP3, necroptosis inhibitor Nec-1 could not alleviate cell death induced by corilagin, indicating necroptosis was not triggered. Subcutaneous tumour growth in nude mice was attenuated by corilagin, consisting with the results in vitro. These results imply that corilagin inhibits cancer cell proliferation through inducing apoptosis and autophagy which regulated by ROS release.

SUBMITTER: Tong Y 

PROVIDER: S-EPMC6050496 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3510816 | BioStudies
2014-01-01 | S-EPMC4278276 | BioStudies
2020-01-01 | S-EPMC7584788 | BioStudies
2012-01-01 | S-EPMC3446972 | BioStudies
2017-01-01 | S-EPMC5462742 | BioStudies
1000-01-01 | S-EPMC3554340 | BioStudies
1000-01-01 | S-EPMC4846877 | BioStudies
2019-01-01 | S-EPMC6522464 | BioStudies
1000-01-01 | S-EPMC6059062 | BioStudies
2016-01-01 | S-EPMC5126308 | BioStudies