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Critical roles for JNK, c-Jun, and Fas/FasL-Signaling in vitamin E analog-induced apoptosis in human prostate cancer cells.
Prostate. 2008 Mar 01; 68(4):427-41.P

Abstract

BACKGROUND

Alpha-tocopherol ether-linked acetic acid (alpha-TEA), an analog of vitamin E (RRR-alpha-tocopherol), is a potent pro-apoptotic agent for human cancer cells in vivo and in vitro.

METHODS

alpha-TEA-induced apoptosis was investigated in LNCaP and PC-3 human prostate cancer cells. Apoptosis was measured by DAPI-staining and FACS analyses of the sub-G1 fraction. Signaling molecules involved in apoptosis were measured by Western immunoblot analyses with or without prior immunoprecipitation, FACS analyses of cell surface membrane expression, RT-PCR analyses of mRNA levels, and chromatin immunoprecipitation. Functional significance was determined using siRNAs, dominant negative mutant, chemical inhibitor, or neutralizing antibody.

RESULTS

Alpha-TEA treatment increased Fas and Fas ligand mRNA and protein levels; as well as, levels of cell surface membrane Fas in both cell lines. Blockage of Fas signaling attenuated alpha-TEA-induced apoptosis. alpha-TEA treatment also produced prolonged, elevated levels of activated (phosphorylated) c-Jun N-terminal kinase (JNK) and its substrate c-Jun, both of which were demonstrated to be necessary for alpha-TEA-induced apoptosis. Chromatin immunoprecipitation results showed binding of c-Jun to the promoters of both Fas and FasL in alpha-TEA treated cells. Investigations of alpha-TEA-triggered apoptosis showed dual signaling from Fas with essential roles for both FADD and Daxx with FADD initiating the classical pathway mediated by caspase-8 activation and Daxx initiating an alternate pathway involving activation of JNK, c-Jun, and increased levels of Fas and FasL.

CONCLUSIONS

Collectively, data support critical roles for JNK, c-Jun, and dual signaling from Fas/FasL via FADD and Daxx in alpha-TEA-induced apoptosis of human prostate cancer cells.

Authors+Show Affiliations

Section of Molecular Genetics and Microbiology, School of Biological Sciences, The University of Texas at Austin, Austin, Texas 78712, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18196534

Citation

Jia, Li, et al. "Critical Roles for JNK, c-Jun, and Fas/FasL-Signaling in Vitamin E Analog-induced Apoptosis in Human Prostate Cancer Cells." The Prostate, vol. 68, no. 4, 2008, pp. 427-41.
Jia L, Yu W, Wang P, et al. Critical roles for JNK, c-Jun, and Fas/FasL-Signaling in vitamin E analog-induced apoptosis in human prostate cancer cells. Prostate. 2008;68(4):427-41.
Jia, L., Yu, W., Wang, P., Li, J., Sanders, B. G., & Kline, K. (2008). Critical roles for JNK, c-Jun, and Fas/FasL-Signaling in vitamin E analog-induced apoptosis in human prostate cancer cells. The Prostate, 68(4), 427-41. https://doi.org/10.1002/pros.20716
Jia L, et al. Critical Roles for JNK, c-Jun, and Fas/FasL-Signaling in Vitamin E Analog-induced Apoptosis in Human Prostate Cancer Cells. Prostate. 2008 Mar 1;68(4):427-41. PubMed PMID: 18196534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical roles for JNK, c-Jun, and Fas/FasL-Signaling in vitamin E analog-induced apoptosis in human prostate cancer cells. AU - Jia,Li, AU - Yu,Weiping, AU - Wang,Pei, AU - Li,Jing, AU - Sanders,Bob G, AU - Kline,Kimberly, PY - 2008/1/16/pubmed PY - 2008/5/1/medline PY - 2008/1/16/entrez SP - 427 EP - 41 JF - The Prostate JO - Prostate VL - 68 IS - 4 N2 - BACKGROUND: Alpha-tocopherol ether-linked acetic acid (alpha-TEA), an analog of vitamin E (RRR-alpha-tocopherol), is a potent pro-apoptotic agent for human cancer cells in vivo and in vitro. METHODS: alpha-TEA-induced apoptosis was investigated in LNCaP and PC-3 human prostate cancer cells. Apoptosis was measured by DAPI-staining and FACS analyses of the sub-G1 fraction. Signaling molecules involved in apoptosis were measured by Western immunoblot analyses with or without prior immunoprecipitation, FACS analyses of cell surface membrane expression, RT-PCR analyses of mRNA levels, and chromatin immunoprecipitation. Functional significance was determined using siRNAs, dominant negative mutant, chemical inhibitor, or neutralizing antibody. RESULTS: Alpha-TEA treatment increased Fas and Fas ligand mRNA and protein levels; as well as, levels of cell surface membrane Fas in both cell lines. Blockage of Fas signaling attenuated alpha-TEA-induced apoptosis. alpha-TEA treatment also produced prolonged, elevated levels of activated (phosphorylated) c-Jun N-terminal kinase (JNK) and its substrate c-Jun, both of which were demonstrated to be necessary for alpha-TEA-induced apoptosis. Chromatin immunoprecipitation results showed binding of c-Jun to the promoters of both Fas and FasL in alpha-TEA treated cells. Investigations of alpha-TEA-triggered apoptosis showed dual signaling from Fas with essential roles for both FADD and Daxx with FADD initiating the classical pathway mediated by caspase-8 activation and Daxx initiating an alternate pathway involving activation of JNK, c-Jun, and increased levels of Fas and FasL. CONCLUSIONS: Collectively, data support critical roles for JNK, c-Jun, and dual signaling from Fas/FasL via FADD and Daxx in alpha-TEA-induced apoptosis of human prostate cancer cells. SN - 0270-4137 UR - https://www.unboundmedicine.com/medline/citation/18196534/Critical_roles_for_JNK_c_Jun_and_Fas/FasL_Signaling_in_vitamin_E_analog_induced_apoptosis_in_human_prostate_cancer_cells_ L2 - https://doi.org/10.1002/pros.20716 DB - PRIME DP - Unbound Medicine ER -