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HA14-1 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: involvement of reactive oxygen species and JNK.
Cancer Lett. 2010 Jun 01; 292(1):111-8.CL

Abstract

Nuclear factor-kappa B (NF-kappaB) activation by tumor necrosis factor-alpha (TNF-alpha) attenuates the TNF-alpha-induced apoptosis pathway. Thus, blockage of NF-kappaB activity may improve the anti-cancer activity of TNF-alpha. HA14-1 induces apoptosis in various human cancer cells, and the molecular mechanisms of this action remain to be fully characterized. The present study evaluated the involvement of NF-kappaB, reactive oxygen species (ROS), and c-Jun N-terminal kinase (JNK) in the effects of HA14-1 by examining the sensitization effect on TNF-alpha-induced apoptosis in human leukemia cells. Such sensitization is closely associated with the inhibitory effect of HA14-1 on TNF-alpha-mediated NF-kappaB activation. HA14-1 suppressed NF-kappaB activation through inhibition of phosphorylation and degradation of IkappaBalpha. This inhibition was correlated with suppression of NF-kappaB-dependent gene products (c-myc, cyclin D1, cox-2, and IAP-1). Additionally, the present findings provide evidence of a critical role of ROS accumulation induced by HA14-1 in TNF-alpha-induced apoptosis. Moreover, HA14-1 also markedly sustained TNF-alpha-mediated JNK activation. A specific JNK inhibitor abolished the sensitization effect of HA14-1 on TNF-alpha-induced apoptosis. Taken together, these results indicate that ROS and JNK represent important signals in HA14-1 sensitization in TNF-alpha-induced apoptosis.

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Authors+Show Affiliations

Moon DO
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea.
Kim MO
No affiliation info available
Kang SH
No affiliation info available
Choi YH
No affiliation info available
Park SY
No affiliation info available
Kim GY
No affiliation info available

MeSH

ApoptosisBenzopyransCell Line, TumorDNA, NeoplasmEnzyme ActivationHumansLeukemiaMAP Kinase Kinase 4NF-kappa BNitrilesReactive Oxygen SpeciesSignal TransductionTumor Necrosis Factor-alpha

Pub Type(s)

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

Language

eng

PubMed ID

20022690

Citation

Moon, Dong-Oh, et al. "HA14-1 Sensitizes TNF-alpha-induced Apoptosis Via Inhibition of the NF-kappaB Signaling Pathway: Involvement of Reactive Oxygen Species and JNK." Cancer Letters, vol. 292, no. 1, 2010, pp. 111-8.
Moon DO, Kim MO, Kang SH, et al. HA14-1 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: involvement of reactive oxygen species and JNK. Cancer Lett. 2010;292(1):111-8.
Moon, D. O., Kim, M. O., Kang, S. H., Choi, Y. H., Park, S. Y., & Kim, G. Y. (2010). HA14-1 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: involvement of reactive oxygen species and JNK. Cancer Letters, 292(1), 111-8. https://doi.org/10.1016/j.canlet.2009.11.014
Moon DO, et al. HA14-1 Sensitizes TNF-alpha-induced Apoptosis Via Inhibition of the NF-kappaB Signaling Pathway: Involvement of Reactive Oxygen Species and JNK. Cancer Lett. 2010 Jun 1;292(1):111-8. PubMed PMID: 20022690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HA14-1 sensitizes TNF-alpha-induced apoptosis via inhibition of the NF-kappaB signaling pathway: involvement of reactive oxygen species and JNK. AU - Moon,Dong-Oh, AU - Kim,Mun-Ock, AU - Kang,Sang-Hyuck, AU - Choi,Yung Hyun, AU - Park,Sung Yong, AU - Kim,Gi-Young, Y1 - 2009/12/22/ PY - 2009/06/30/received PY - 2009/09/22/revised PY - 2009/11/19/accepted PY - 2009/12/22/entrez PY - 2009/12/22/pubmed PY - 2010/4/22/medline SP - 111 EP - 8 JF - Cancer letters JO - Cancer Lett VL - 292 IS - 1 N2 - Nuclear factor-kappa B (NF-kappaB) activation by tumor necrosis factor-alpha (TNF-alpha) attenuates the TNF-alpha-induced apoptosis pathway. Thus, blockage of NF-kappaB activity may improve the anti-cancer activity of TNF-alpha. HA14-1 induces apoptosis in various human cancer cells, and the molecular mechanisms of this action remain to be fully characterized. The present study evaluated the involvement of NF-kappaB, reactive oxygen species (ROS), and c-Jun N-terminal kinase (JNK) in the effects of HA14-1 by examining the sensitization effect on TNF-alpha-induced apoptosis in human leukemia cells. Such sensitization is closely associated with the inhibitory effect of HA14-1 on TNF-alpha-mediated NF-kappaB activation. HA14-1 suppressed NF-kappaB activation through inhibition of phosphorylation and degradation of IkappaBalpha. This inhibition was correlated with suppression of NF-kappaB-dependent gene products (c-myc, cyclin D1, cox-2, and IAP-1). Additionally, the present findings provide evidence of a critical role of ROS accumulation induced by HA14-1 in TNF-alpha-induced apoptosis. Moreover, HA14-1 also markedly sustained TNF-alpha-mediated JNK activation. A specific JNK inhibitor abolished the sensitization effect of HA14-1 on TNF-alpha-induced apoptosis. Taken together, these results indicate that ROS and JNK represent important signals in HA14-1 sensitization in TNF-alpha-induced apoptosis. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/20022690/HA14_1_sensitizes_TNF_alpha_induced_apoptosis_via_inhibition_of_the_NF_kappaB_signaling_pathway:_involvement_of_reactive_oxygen_species_and_JNK_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(09)00684-3 DB - PRIME DP - Unbound Medicine ER -

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