Rhein induces apoptosis in L-02 cells via reactive oxygen species-independent endoplasmic reticulum stress pathway

WANG Dandan; KORAMAGAZI Arouna; MAO Yong; YU Feng

doi:10.11665/j.issn.1000-5048.20160215

Journal of China Pharmaceutical University > 2016 > 47(2): 215-221. > DOI: 10.11665/j.issn.1000-5048.20160215

WANG Dandan, KORAMAGAZI Arouna, MAO Yong, YU Feng. Rhein induces apoptosis in L-02 cells via reactive oxygen species-independent endoplasmic reticulum stress pathway[J]. Journal of China Pharmaceutical University, 2016, 47(2): 215-221. DOI: 10.11665/j.issn.1000-5048.20160215

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Rhein induces apoptosis in L-02 cells via reactive oxygen species-independent endoplasmic reticulum stress pathway

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Abstract

This research aimed to investigate the apoptotic effect of rhein on human primary liver cells(L-02)and the underlying mechanisms. MTT assay was used to detect the inhibitory activity of rhein on L-02 cells. Rhein-induced apoptosis in L-02 cells was evaluated by flow cytometry. Intracellular reactive oxygen species(ROS)was detected by DCFH-DA fluorescent probe. Endoplasmic reticulum stress-related gene and protein expression were detected by real-time quantitative PCR(RT-qPCR)and Western blot. The effect of antioxidant N-acetylcysteine(NAC)on these proteins, cysteinyl aspartate specific proteinase 4(caspase-4)and cysteinyl aspartate specific proteinase 3(caspase-3)activity was explored. The results showed that rhein inhibited the viability of L-02 cells in a dose-dependent and time-dependent manners. The apoptosis rate of L-02 cells in rhein-treated groups was increased significantly. Rhein induced generation of ROS which was blocked by NAC. The expressions of GRP 78, ATF-4, CHOP mRNA and the expressions of GRP 78, p-JNK, CHOP proteins were significantly increased in rhein-treated groups. However, NAC could not attenuate the expressions of GRP 78, p-JNK, CHOP proteins, caspase-4, caspase-3 activity induced by rhein significantly. In conclusion, rhein induces apoptosis in L-02 cells via a reactive oxygen species-independent endoplasmic reticulum stress pathway.
- rhein,
- L-02 cells,
- apoptosis,
- endoplasmic reticulum stress,
- reactive oxygen species

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[1]	Zimmerman HJ.Drug-induced liver disease[J].Clin Liver Dis,2000,4(1):73-96.
[2]	Zhang ZF,Zhao G.Chronologial evolvement of the etiology of drug-induced liver injury in China:a meta-analysis[J].Med Philosophy(医学与哲学),2013,34(10B):9-13.
[3]	Huang LJ,Qian XQ,Shen ZL.Clinical analysis of 19 cases of liver injury induced by Polygonum and its preparations[J].Zhejiang J Integr Tradit Chin West Med(浙江中西医结合杂志),2015,24(4):407-408.
[4]	Li XH,Li M,Tao YR.Development of pharmacological effects of rhein and its derivatives[J].Drugs Clinic(现代药物与临床),2010,25(6):417-421.
[5]	He LN,Yang AH,Cui TY,et al.Reactive metabolite activation by CYP2C19-mediated rhein hepatotoxicity[J].Xenobiotica,2015,45(4):361-372.
[6]	Li JS,Wang WJ,Sun Y,et al.Ursolic acid inhibits the development of nonalcoholic fatty liver disease by attenuating endoplasmic reticulum stress[J].Food Funct,2015,6(5):1643-1651.
[7]	Lai WW,Yang JS,Lai KC,et al.Rhein induced apoptosis through the endoplasmic reticulum stress,caspase-and mitochondria-dependent pathways in SCC-4 human tongue squamous cancer cells[J].In Vivo,2009,23(2):309-316.
[8]	Hsia TC, Yang JS, Chen GW, et al. The roles of endoplasmic reticulum stress and Ca²⁺ on rhein-induced apoptosis in A-549 human lung cancer cells[J].Anticancer Res,2009,29(1):309-318.
[9]	Sun H,Yang JP,Mao Y,et al.Involvement of Fas-dependent pathway in rhein-induced apoptosis of Hk-2 cells[J].J China Pharm Univ(中国药科大学学报),2015,46(4):469-475.
[10]	Du Q,Bian XL,Xu XL,et al.Role of mitochondrial permeability transition in human hepatocellular carcinoma Hep-G2 cell death induced by rhein[J].Fitoterapia,2013,91(8):68-73.
[11]	Lee JH,Jo YH,Kim K,et al.Effect of N-acetyicysteine(NAC)on acute lung injury andacute kidney injury in hemorrhagic shock[J].Resuscitation,2013,84(1):121-127.
[12]	Kim I,Xu W,Reed JC.Cell death and endoplasmic reticulum stress:disease relevance and therapeutic opportunities[J].Nat Rev Drug Discov,2008,7(12):1013-1030.
[13]	Wang X,Eno CO,Altman BJ,et al.ER stress modulates cellular metabolism[J].Biochem J,2011,435(1):285-296.
[14]	Wu F,An YK,Zhu YQ.Research progress of tumor cell apoptosis and endoplasmic reticulum stress[J].J Mod Oncol(现代肿瘤医学),2014,22(9):2228-2231.
[15]	Chao L,Jin W,Ying L,et al.Transmembrane protein 214(TMEM214)mediates endoplasmic reticulum stress-induced caspase 4 enzyme activation and apoptosis[J].J Biol Chem,2013,288(24):17908-17917.
[16]	Quan Z,Gu J,Dong P,et al.Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to cirsimaritin-induced apoptosis in human gallbladder carcinoma GBC-SD cells[J].Cancer Lett,2010,295(2):252-259.
[17]	Yang Z,Qiang L,Wu T,et al.Reactive oxygen species-mitochondriapathway involved in FV-429-inducedapoptosisin human hepatocellular carcinoma HepG2 cells[J].Anticancer Drugs,2011,22(9):886-895.
[18]	Lopes RA,Neves KB,Pestana CR,et al.Testosterone inducesapoptosisin vascular smooth muscle cells via extrinsic apoptotic pathway withmitochondria-generatedreactive oxygen speciesinvolvement[J].Am J Physiol Heart Circ Physiol,2014,306(11):H1485-1494.

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Rhein induces apoptosis in L-02 cells via reactive oxygen species-independent endoplasmic reticulum stress pathway

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