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Inhibition of nuclear factor kappaB induces apoptosis following treatment with tumor necrosis factor alpha and an antioxidant in human prostate cancer cells.
Cancer Detect Prev. 2002; 26(3):229-37.CD

Abstract

Transforming growth factor beta-1 (TGFbeta-1) and tumor necrosis factor alpha (TNF-alpha), an activator of nuclear factor kappa B (NF-kappaB), modulate apoptosis and/or cell growth. This study was designed to investigate the activity of NF-kappaB and its regulation of inhibitor of apoptosis gene (c-IAP2) in two human prostate cancer cell lines, DU-145 (which is androgen unresponsive) and ALVA-101 (which is moderately androgen responsive). These cells were treated with and without various concentrations of a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), and TNF-alpha at various time intervals. Following treatments, cell growth and apoptosis were determined by ELISA techniques. NF-kappaB activity was determined by electrophoretic mobility shift assay (EMSA), and c-IAP2 mRNA production was determined with Northern blot analysis. PDTC treatment significantly reduced cell growth up to 80% in both DU-145 and ALVA-101 cells. TNF-alpha and lower but not higher doses of PDTC combined demonstrated an additive inhibition of cell growth in both cell lines. Active NF-kappaB and c-IAP2 was blocked significantly following PDTC treatments, whereas treatments with TNF-alpha alone showed increased NF-kappaB activity and c-IAP2. However, when both PDTC and TNF-alpha were combined, nuclear presence of NF-kappaB and c-IAP2 were reduced significantly (P < 0.05) to levels observed with PDTC alone. In conclusion, the antioxidant, PDTC, appears to initiate apoptosis by blocking cytoplasmic NF-kappaB translocation to the nucleus where it normally activates the production of apoptosis-inhibitory proteins like c-IAP2. Both TNF-alpha and PDTC alone cause apoptosis and reduce cell growth, but their combined effects are additive in reducing cell growth of DU-145 and ALVA-101 human prostate cancer cells.

Authors+Show Affiliations

Department of Medicine and Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12269771

Citation

Gunawardena, Kushlani, et al. "Inhibition of Nuclear Factor kappaB Induces Apoptosis Following Treatment With Tumor Necrosis Factor Alpha and an Antioxidant in Human Prostate Cancer Cells." Cancer Detection and Prevention, vol. 26, no. 3, 2002, pp. 229-37.
Gunawardena K, Murray DK, Swope RE, et al. Inhibition of nuclear factor kappaB induces apoptosis following treatment with tumor necrosis factor alpha and an antioxidant in human prostate cancer cells. Cancer Detect Prev. 2002;26(3):229-37.
Gunawardena, K., Murray, D. K., Swope, R. E., & Meikle, A. W. (2002). Inhibition of nuclear factor kappaB induces apoptosis following treatment with tumor necrosis factor alpha and an antioxidant in human prostate cancer cells. Cancer Detection and Prevention, 26(3), 229-37.
Gunawardena K, et al. Inhibition of Nuclear Factor kappaB Induces Apoptosis Following Treatment With Tumor Necrosis Factor Alpha and an Antioxidant in Human Prostate Cancer Cells. Cancer Detect Prev. 2002;26(3):229-37. PubMed PMID: 12269771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of nuclear factor kappaB induces apoptosis following treatment with tumor necrosis factor alpha and an antioxidant in human prostate cancer cells. AU - Gunawardena,Kushlani, AU - Murray,Darrell K, AU - Swope,Richard E, AU - Meikle,A Wayne, PY - 2002/9/25/pubmed PY - 2003/4/18/medline PY - 2002/9/25/entrez SP - 229 EP - 37 JF - Cancer detection and prevention JO - Cancer Detect Prev VL - 26 IS - 3 N2 - Transforming growth factor beta-1 (TGFbeta-1) and tumor necrosis factor alpha (TNF-alpha), an activator of nuclear factor kappa B (NF-kappaB), modulate apoptosis and/or cell growth. This study was designed to investigate the activity of NF-kappaB and its regulation of inhibitor of apoptosis gene (c-IAP2) in two human prostate cancer cell lines, DU-145 (which is androgen unresponsive) and ALVA-101 (which is moderately androgen responsive). These cells were treated with and without various concentrations of a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), and TNF-alpha at various time intervals. Following treatments, cell growth and apoptosis were determined by ELISA techniques. NF-kappaB activity was determined by electrophoretic mobility shift assay (EMSA), and c-IAP2 mRNA production was determined with Northern blot analysis. PDTC treatment significantly reduced cell growth up to 80% in both DU-145 and ALVA-101 cells. TNF-alpha and lower but not higher doses of PDTC combined demonstrated an additive inhibition of cell growth in both cell lines. Active NF-kappaB and c-IAP2 was blocked significantly following PDTC treatments, whereas treatments with TNF-alpha alone showed increased NF-kappaB activity and c-IAP2. However, when both PDTC and TNF-alpha were combined, nuclear presence of NF-kappaB and c-IAP2 were reduced significantly (P < 0.05) to levels observed with PDTC alone. In conclusion, the antioxidant, PDTC, appears to initiate apoptosis by blocking cytoplasmic NF-kappaB translocation to the nucleus where it normally activates the production of apoptosis-inhibitory proteins like c-IAP2. Both TNF-alpha and PDTC alone cause apoptosis and reduce cell growth, but their combined effects are additive in reducing cell growth of DU-145 and ALVA-101 human prostate cancer cells. SN - 0361-090X UR - https://www.unboundmedicine.com/medline/citation/12269771/Inhibition_of_nuclear_factor_kappaB_induces_apoptosis_following_treatment_with_tumor_necrosis_factor_alpha_and_an_antioxidant_in_human_prostate_cancer_cells_ L2 - http://www.diseaseinfosearch.org/result/9175 DB - PRIME DP - Unbound Medicine ER -