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Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells.
J Agric Food Chem. 2014 Jun 11; 62(23):5390-400.JA

Abstract

Cell death is closely related to autophagy under some circumstances; however, the effect of isoorientin (ISO) on autophagy and the interplay between apoptosis and autophagy in human hepatoblastoma cancer (HepG2) cells remains poorly understood. The present study showed that ISO induced autophagy, which was correlated with the formation of autophagic vacuoles and the overexpression of Beclin-1 and LC3-II. The autophagy inhibitor 3-methyladenine (3-MA) markedly inhibited apoptosis, and the apoptosis inhibitor ZVAD-fmk also decreased ISO-induced autophagy. In addition, the PI3K/Akt inhibitor LY294002 enhanced Beclin-1, LC3-II, and poly(ADP-ribose) polymerase (PARP) cleavage levels. Also, the reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine (NAC), the JNK inhibitor SP600125, and the p38 inhibitor SB203580 efficiently downregulated the levels of these proteins. Moreover, the p53 inhibitor pifithrin-α and the nuclear factor (NF)-κB inhibitor pyrrolidinedithiocarbamic acid (PDTC) clearly suppressed Beclin-1 and LC3-II and increased cytochrome c release, caspase-3 activation, and PARP cleavage. These results demonstrated for the first time that ISO simultaneously induced apoptosis and autophagy by ROS-related p53, PI3K/Akt, JNK, and p38 signaling pathways. Furthermore, ISO-induced apoptosis by activating the Fas receptor-mediated apoptotic pathway and suppressing the p53 and PI3K/Akt-dependent NF-κB signaling pathway, with the subsequent increase in the release of cytochrome c, caspase-3 activation, and PARP cleavage.

Authors+Show Affiliations

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest Agriculture and Forestry (A&F) University , Yangling, Shaanxi 712100, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24841907

Citation

Yuan, Li, et al. "Isoorientin Induces Apoptosis and Autophagy Simultaneously By Reactive Oxygen Species (ROS)-related P53, PI3K/Akt, JNK, and P38 Signaling Pathways in HepG2 Cancer Cells." Journal of Agricultural and Food Chemistry, vol. 62, no. 23, 2014, pp. 5390-400.
Yuan L, Wei S, Wang J, et al. Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. J Agric Food Chem. 2014;62(23):5390-400.
Yuan, L., Wei, S., Wang, J., & Liu, X. (2014). Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. Journal of Agricultural and Food Chemistry, 62(23), 5390-400. https://doi.org/10.1021/jf500903g
Yuan L, et al. Isoorientin Induces Apoptosis and Autophagy Simultaneously By Reactive Oxygen Species (ROS)-related P53, PI3K/Akt, JNK, and P38 Signaling Pathways in HepG2 Cancer Cells. J Agric Food Chem. 2014 Jun 11;62(23):5390-400. PubMed PMID: 24841907.
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TY - JOUR T1 - Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. AU - Yuan,Li, AU - Wei,Shuping, AU - Wang,Jing, AU - Liu,Xuebo, Y1 - 2014/06/03/ PY - 2014/5/21/entrez PY - 2014/5/21/pubmed PY - 2015/1/22/medline SP - 5390 EP - 400 JF - Journal of agricultural and food chemistry JO - J Agric Food Chem VL - 62 IS - 23 N2 - Cell death is closely related to autophagy under some circumstances; however, the effect of isoorientin (ISO) on autophagy and the interplay between apoptosis and autophagy in human hepatoblastoma cancer (HepG2) cells remains poorly understood. The present study showed that ISO induced autophagy, which was correlated with the formation of autophagic vacuoles and the overexpression of Beclin-1 and LC3-II. The autophagy inhibitor 3-methyladenine (3-MA) markedly inhibited apoptosis, and the apoptosis inhibitor ZVAD-fmk also decreased ISO-induced autophagy. In addition, the PI3K/Akt inhibitor LY294002 enhanced Beclin-1, LC3-II, and poly(ADP-ribose) polymerase (PARP) cleavage levels. Also, the reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine (NAC), the JNK inhibitor SP600125, and the p38 inhibitor SB203580 efficiently downregulated the levels of these proteins. Moreover, the p53 inhibitor pifithrin-α and the nuclear factor (NF)-κB inhibitor pyrrolidinedithiocarbamic acid (PDTC) clearly suppressed Beclin-1 and LC3-II and increased cytochrome c release, caspase-3 activation, and PARP cleavage. These results demonstrated for the first time that ISO simultaneously induced apoptosis and autophagy by ROS-related p53, PI3K/Akt, JNK, and p38 signaling pathways. Furthermore, ISO-induced apoptosis by activating the Fas receptor-mediated apoptotic pathway and suppressing the p53 and PI3K/Akt-dependent NF-κB signaling pathway, with the subsequent increase in the release of cytochrome c, caspase-3 activation, and PARP cleavage. SN - 1520-5118 UR - https://www.unboundmedicine.com/medline/citation/24841907/Isoorientin_induces_apoptosis_and_autophagy_simultaneously_by_reactive_oxygen_species__ROS__related_p53_PI3K/Akt_JNK_and_p38_signaling_pathways_in_HepG2_cancer_cells_ L2 - https://doi.org/10.1021/jf500903g DB - PRIME DP - Unbound Medicine ER -