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[PMID]: | 29328482 | [Au] Autor: | Yu L; Jiang B; Chen Z; Wang X; Shang D; Zhang X; Sun Y; Yang J; Ji Y |
[Ad] Address: | Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin, Heilongjiang 150076, P.R. China. | [Ti] Title: | Cytisine induces endoplasmic reticulum stress caused by calcium overload in HepG2 cells. | [So] Source: | Oncol Rep;39(3):1475-1484, 2018 Mar. | [Is] ISSN: | 1791-2431 | [Cp] Country of publication: | Greece | [La] Language: | eng | [Ab] Abstract: | Cytisine, a quinolizidine alkaloid, is one of the major bioactive components found in the small tree Sophora Alopecuraides L., and is a traditional Chinese medicine that is used for treating hepatitis and liver cancer. In the 1960s, quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour cell proliferation in several types of cancer cells. However, few studies have investigated the effect of cytisine on liver cancer. Our team confirmed that cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway. The primary aim of the present study was to evaluate the endoplasmic reticulum (ER) stress caused by calcium overload in cytisineinduced apoptosis in HepG2 cells and the molecular mechanisms of this phenomenon. In addition, the present study was undertaken to evaluate the expression of α7nAChR when apoptosis was induced by cytisine in HepG2 cells. In the present study, transmission electron microscopy was used to observe the morphological appearance of HepG2 cells. The apoptosis of the cells with cytoplasmic vacuolization was significant under electron microscopy. Apoptotic bodies, the expansion of the ER, and swelling of mitochondria were observed in the HepG2 cells after cytisine treatment. Flow cytometric analysis demonstrated that the apoptosis rate of HepG2 cells was upregulated. In addition, the intracellular calcium concentration was detected by laser confocal fluorescence microscopy. The laser confocal fluorescence microscopy showed that the calcium concentration was increased in a dosedependent manner. The activity of caspase4 was evaluated by an enzymelinked analyser, and the expression levels of CHOP, JNK, pJNK and α7nAChR were assessed via western blot analysis. In the present study, we observed that cytisine induced ER stressinducing factors and CHOP and pJNK1/2 protein expression, and it increased the JNK protein expression in the HepG2 cells. Furthermore, α7nAChR protein expression was promoted in a dosedependent manner after cytisine treatment. These findings suggest that cytisine induced the ER stressmediated apoptotic pathway via activation of CHOP, JNK and caspase4 in HepG2 cells, and cytisine is a potential new target compound for nAchRs (nicotinic acetylcholine receptors) to treat liver cancer. | [Pt] Publication type: | JOURNAL ARTICLE | [Em] Entry month: | 1801 | [Cu] Class update date: |
180202 | [Lr] Last revision date: | 180202 | [St] Status: | In-Process |
[do] DOI: | 10.3892/or.2018.6200 |
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