Unknown

Dataset Information

0

Chalcomoracin inhibits cell proliferation and increases sensitivity to radiotherapy in human non-small cell lung cancer cells via inducing endoplasmic reticulum stress-mediated paraptosis.


ABSTRACT: Chalcomoracin (CMR) is a kind of Diels-Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low and median doses of CMR induced paraptosis but not apoptosis, which was presented as the formation of extensive cytoplasmic vacuolation with increased expression of endoplasmic reticulum stress markers, Bip and Chop, as well as activation of MAPK pathway in the lung cancer cells. Knockdown of Bip with siRNA not only reduced the cell-killing effect of CMR, but also decreased the percentage of cytoplasmic vacuoles in H460 cells. Moreover, CMR also increased the sensitivity of lung cancer cells to radiotherapy through enhanced endoplasmic reticulum stress. In lung cancer H460 cell xenograft nude mice, combined treatment of CMR and radiation caused greatly enhanced tumor growth inhibition with upregulation of endoplasmic reticulum stress proteins and activation of pErk in xenograft tumor tissue. These data demonstrate that the anticancer activity and radiosensitization effect of CMR result from inducing paraptosis, suggesting that CMR could be considered as a potential anticancer agent and radiation sensitizer in the future cancer therapeutics.

SUBMITTER: Zhang SR 

PROVIDER: S-EPMC7470873 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Chalcomoracin inhibits cell proliferation and increases sensitivity to radiotherapy in human non-small cell lung cancer cells via inducing endoplasmic reticulum stress-mediated paraptosis.

Zhang Shi-Rong SR   Zhang Xiao-Chen XC   Liang Jia-Feng JF   Fang Hong-Ming HM   Huang Hai-Xiu HX   Zhao Yan-Yan YY   Chen Xue-Qin XQ   Ma Sheng-Lin SL  

Acta pharmacologica Sinica 20200217 6


Chalcomoracin (CMR) is a kind of Diels-Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low  ...[more]

Similar Datasets

| S-EPMC8311285 | biostudies-literature
| S-EPMC3551933 | biostudies-literature
| S-EPMC11312418 | biostudies-literature
| S-EPMC6944487 | biostudies-literature
| S-EPMC5762097 | biostudies-literature
| S-EPMC5689693 | biostudies-literature
| S-EPMC5593615 | biostudies-literature
| S-EPMC10560440 | biostudies-literature
| S-EPMC5584615 | biostudies-literature
| S-EPMC10965266 | biostudies-literature