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Effects of antioxidants and caspase-3 inhibitor on the phenylethyl isothiocyanate-induced apoptotic signaling pathways in human PLC/PRF/5 cells.
Eur J Pharmacol. 2005 Aug 22; 518(2-3):96-106.EJ

Abstract

Phenylethyl isothiocyanate (PEITC) is a well recognized potential chemopreventive compound against human cancers. In this study, the molecular mechanism of PEITC-induced apoptosis was examined with two antioxidants (N-acetyl-cysteine and vitamin E) and a caspase-3 inhibitor (z-DEVD-fmk). Results demonstrated that PEITC significantly induced human hepatoma PLC/PRF/5 (CD95-negative) cells undergoing apoptosis. Treatment with 0 approximately 10 microM PEITC-triggered cell apoptosis as revealed by the externalization of annexin V-targeted phosphatidylserine and the subsequent appearance of sub-G1 population. Results also displayed that PEITC-induced apoptosis involves the up-regulation of p53 and Bax protein, down-regulation of the XIAP, Bcl-2, Bcl-(XL) and Mcl-1 proteins, cleavage of Bid, and the release of cytochrome c and Smac/Diablo, which were accompanied by the activation of caspases -9, -3 and -8. PEITC-induced the generation of reactive oxygen species and the decrease of mitochondrial membrane potential (Deltapsim) in a time-dependent pattern. N-acetyl-cysteine and vitamin E at 100 microM, and z-DEVD-fmk at 50 microM markedly blocked PEITC-induced apoptosis, which was demonstrated by a decline in the reactive oxygen species generation and the release of the cytochrome c and Smac/Diablo from mitochondria to the cytosol. N-acetyl-cysteine, vitamin E and z-DEVD-fmk also prevented the PEITC in inducing the loss of Deltapsim. They also affected the activity of XIAP and Bax proteins. Taken together, these studies suggest that PEITC is an apoptotic inducer that acts on the mitochondria and the feedback amplification loop of caspase-8/Bid pathways in PLC/PRF/5 cells.

Authors+Show Affiliations

Graduate Institute of Natural products, College of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16054126

Citation

Wu, Shu-Jing, et al. "Effects of Antioxidants and Caspase-3 Inhibitor On the Phenylethyl Isothiocyanate-induced Apoptotic Signaling Pathways in Human PLC/PRF/5 Cells." European Journal of Pharmacology, vol. 518, no. 2-3, 2005, pp. 96-106.
Wu SJ, Ng LT, Lin CC. Effects of antioxidants and caspase-3 inhibitor on the phenylethyl isothiocyanate-induced apoptotic signaling pathways in human PLC/PRF/5 cells. Eur J Pharmacol. 2005;518(2-3):96-106.
Wu, S. J., Ng, L. T., & Lin, C. C. (2005). Effects of antioxidants and caspase-3 inhibitor on the phenylethyl isothiocyanate-induced apoptotic signaling pathways in human PLC/PRF/5 cells. European Journal of Pharmacology, 518(2-3), 96-106.
Wu SJ, Ng LT, Lin CC. Effects of Antioxidants and Caspase-3 Inhibitor On the Phenylethyl Isothiocyanate-induced Apoptotic Signaling Pathways in Human PLC/PRF/5 Cells. Eur J Pharmacol. 2005 Aug 22;518(2-3):96-106. PubMed PMID: 16054126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of antioxidants and caspase-3 inhibitor on the phenylethyl isothiocyanate-induced apoptotic signaling pathways in human PLC/PRF/5 cells. AU - Wu,Shu-Jing, AU - Ng,Lean Teik, AU - Lin,Chun-Ching, PY - 2005/05/12/received PY - 2005/06/14/revised PY - 2005/06/20/accepted PY - 2005/8/2/pubmed PY - 2005/9/24/medline PY - 2005/8/2/entrez SP - 96 EP - 106 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 518 IS - 2-3 N2 - Phenylethyl isothiocyanate (PEITC) is a well recognized potential chemopreventive compound against human cancers. In this study, the molecular mechanism of PEITC-induced apoptosis was examined with two antioxidants (N-acetyl-cysteine and vitamin E) and a caspase-3 inhibitor (z-DEVD-fmk). Results demonstrated that PEITC significantly induced human hepatoma PLC/PRF/5 (CD95-negative) cells undergoing apoptosis. Treatment with 0 approximately 10 microM PEITC-triggered cell apoptosis as revealed by the externalization of annexin V-targeted phosphatidylserine and the subsequent appearance of sub-G1 population. Results also displayed that PEITC-induced apoptosis involves the up-regulation of p53 and Bax protein, down-regulation of the XIAP, Bcl-2, Bcl-(XL) and Mcl-1 proteins, cleavage of Bid, and the release of cytochrome c and Smac/Diablo, which were accompanied by the activation of caspases -9, -3 and -8. PEITC-induced the generation of reactive oxygen species and the decrease of mitochondrial membrane potential (Deltapsim) in a time-dependent pattern. N-acetyl-cysteine and vitamin E at 100 microM, and z-DEVD-fmk at 50 microM markedly blocked PEITC-induced apoptosis, which was demonstrated by a decline in the reactive oxygen species generation and the release of the cytochrome c and Smac/Diablo from mitochondria to the cytosol. N-acetyl-cysteine, vitamin E and z-DEVD-fmk also prevented the PEITC in inducing the loss of Deltapsim. They also affected the activity of XIAP and Bax proteins. Taken together, these studies suggest that PEITC is an apoptotic inducer that acts on the mitochondria and the feedback amplification loop of caspase-8/Bid pathways in PLC/PRF/5 cells. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16054126/Effects_of_antioxidants_and_caspase_3_inhibitor_on_the_phenylethyl_isothiocyanate_induced_apoptotic_signaling_pathways_in_human_PLC/PRF/5_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(05)00673-4 DB - PRIME DP - Unbound Medicine ER -