Tags

Type your tag names separated by a space and hit enter

Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells.
Cancer Res 2001; 61(17):6569-76CR

Abstract

RRR-alpha-tocopherol succinate (vitamin E succinate, VES) is a potent, selective apoptotic agent for cancer cells but not normal cells. VES has been shown to inhibit the growth of a wide variety of tumor cells in cell culture and animal models. Studies addressing mechanisms of action of VES-induced apoptosis have identified transforming growth factor-beta, Fas/CD95-APO-1, and mitogen-activated protein kinase (MAPK) signaling pathway involvement. Here we show that MAPKs, the extracellular signal-regulated kinases (ERK), and the stress-activated protein kinases, c-Jun NH2-terminal kinases (JNK), but not p38, are critical mediators in VES-induced apoptosis of human breast cancer MDA-MB-435 cells. VES activates ERK1/2 and JNK both in level and duration of kinase activity. Expression of dominant negative mutants of ERK1, MAPK/ERK activator-1, or JNK1 but not p38 blocked phosphorylation of the substrate glutathione S-transferase-c-Jun and inhibited VES-induced apoptosis. Increased phosphorylation and transactivation activity of nuclear transcription factors c-Jun, ATF-2, and Elk-1 are observed after VES treatments; however, only c-Jun and ATF-2 appear to be involved in VES-induced apoptosis based on antisense blockage experiments. Collectively, these results imply a critical role for ERK1 and JNK1 but not p38 in VES-induced apoptosis of human MDA-MB-435 breast cancer cells.

Authors+Show Affiliations

Division of Nutrition/A2703, University of Texas at Austin, 78712, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11522656

Citation

Yu, W, et al. "Activation of Extracellular Signal-regulated Kinase and c-Jun-NH(2)-terminal Kinase but Not P38 Mitogen-activated Protein Kinases Is Required for RRR-alpha-tocopheryl Succinate-induced Apoptosis of Human Breast Cancer Cells." Cancer Research, vol. 61, no. 17, 2001, pp. 6569-76.
Yu W, Liao QY, Hantash FM, et al. Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells. Cancer Res. 2001;61(17):6569-76.
Yu, W., Liao, Q. Y., Hantash, F. M., Sanders, B. G., & Kline, K. (2001). Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells. Cancer Research, 61(17), pp. 6569-76.
Yu W, et al. Activation of Extracellular Signal-regulated Kinase and c-Jun-NH(2)-terminal Kinase but Not P38 Mitogen-activated Protein Kinases Is Required for RRR-alpha-tocopheryl Succinate-induced Apoptosis of Human Breast Cancer Cells. Cancer Res. 2001 Sep 1;61(17):6569-76. PubMed PMID: 11522656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells. AU - Yu,W, AU - Liao,Q Y, AU - Hantash,F M, AU - Sanders,B G, AU - Kline,K, PY - 2001/8/28/pubmed PY - 2001/9/14/medline PY - 2001/8/28/entrez SP - 6569 EP - 76 JF - Cancer research JO - Cancer Res. VL - 61 IS - 17 N2 - RRR-alpha-tocopherol succinate (vitamin E succinate, VES) is a potent, selective apoptotic agent for cancer cells but not normal cells. VES has been shown to inhibit the growth of a wide variety of tumor cells in cell culture and animal models. Studies addressing mechanisms of action of VES-induced apoptosis have identified transforming growth factor-beta, Fas/CD95-APO-1, and mitogen-activated protein kinase (MAPK) signaling pathway involvement. Here we show that MAPKs, the extracellular signal-regulated kinases (ERK), and the stress-activated protein kinases, c-Jun NH2-terminal kinases (JNK), but not p38, are critical mediators in VES-induced apoptosis of human breast cancer MDA-MB-435 cells. VES activates ERK1/2 and JNK both in level and duration of kinase activity. Expression of dominant negative mutants of ERK1, MAPK/ERK activator-1, or JNK1 but not p38 blocked phosphorylation of the substrate glutathione S-transferase-c-Jun and inhibited VES-induced apoptosis. Increased phosphorylation and transactivation activity of nuclear transcription factors c-Jun, ATF-2, and Elk-1 are observed after VES treatments; however, only c-Jun and ATF-2 appear to be involved in VES-induced apoptosis based on antisense blockage experiments. Collectively, these results imply a critical role for ERK1 and JNK1 but not p38 in VES-induced apoptosis of human MDA-MB-435 breast cancer cells. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11522656/Activation_of_extracellular_signal_regulated_kinase_and_c_Jun_NH_2__terminal_kinase_but_not_p38_mitogen_activated_protein_kinases_is_required_for_RRR_alpha_tocopheryl_succinate_induced_apoptosis_of_human_breast_cancer_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11522656 DB - PRIME DP - Unbound Medicine ER -