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Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-{kappa}B activation in the glucocorticoid receptor-rich human cervical carcinoma cell line SiHa.
J Endocrinol. 2006 Feb; 188(2):311-9.JE

Abstract

Glucocorticoids (GCs) are commonly co-administered with cisplatin in the treatment of patients with carcinomas to prevent drug-induced allergic reaction, nausea and vomiting. Although GC receptor (GR) is ubiquitous in carcinoma cells and has been linked to signal transduction pathways pertinent to cell growth and apoptosis, little is known regarding the possible effect of GC on the chemosensitivity of carcinomas. Our previous study demonstrated that dexamethasone (DEX) enhances the cytotoxicity to cisplatin in a GR-rich human cervical carcinoma cell line, SiHa. In this study, we found that this cisplatin cytotoxicity-enhancing effect of DEX correlated well with its effect on abrogating the cisplatin-induced activation of nuclear factor kappa B (NF-kappaB). RU486, a structural homologue of DEX, partially reversed this cytotoxicity-enhancing effect of DEX, a finding consistent with the well-known partial reversing effect of RU486 on DEX-induced NF-kappaB suppression. Furthermore, expression of a dominant-negative truncated IkappaBalpha gene in SiHa cells completely abolished the cisplatin cytotoxicity-enhancing effect of DEX. Our data suggest that the specific action of DEX on GR may enhance the cytotoxicity of cisplatin in selected GR-rich cancer cells by suppressing NF-kappaB activation.

Authors+Show Affiliations

Department of Oncology, National Taiwan University Hospital, No. 7 Chung-Shan South Rd, Taipei 10016, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16461557

Citation

Lu, Yen-Shen, et al. "Glucocorticoids Enhance Cytotoxicity of Cisplatin Via Suppression of NF-{kappa}B Activation in the Glucocorticoid Receptor-rich Human Cervical Carcinoma Cell Line SiHa." The Journal of Endocrinology, vol. 188, no. 2, 2006, pp. 311-9.
Lu YS, Yeh PY, Chuang SE, et al. Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-{kappa}B activation in the glucocorticoid receptor-rich human cervical carcinoma cell line SiHa. J Endocrinol. 2006;188(2):311-9.
Lu, Y. S., Yeh, P. Y., Chuang, S. E., Gao, M., Kuo, M. L., & Cheng, A. L. (2006). Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-{kappa}B activation in the glucocorticoid receptor-rich human cervical carcinoma cell line SiHa. The Journal of Endocrinology, 188(2), 311-9.
Lu YS, et al. Glucocorticoids Enhance Cytotoxicity of Cisplatin Via Suppression of NF-{kappa}B Activation in the Glucocorticoid Receptor-rich Human Cervical Carcinoma Cell Line SiHa. J Endocrinol. 2006;188(2):311-9. PubMed PMID: 16461557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-{kappa}B activation in the glucocorticoid receptor-rich human cervical carcinoma cell line SiHa. AU - Lu,Yen-Shen, AU - Yeh,Pei-Yen, AU - Chuang,Shuang-En, AU - Gao,Ming, AU - Kuo,Min-Liang, AU - Cheng,Ann-Lii, PY - 2006/2/8/pubmed PY - 2006/4/6/medline PY - 2006/2/8/entrez SP - 311 EP - 9 JF - The Journal of endocrinology JO - J Endocrinol VL - 188 IS - 2 N2 - Glucocorticoids (GCs) are commonly co-administered with cisplatin in the treatment of patients with carcinomas to prevent drug-induced allergic reaction, nausea and vomiting. Although GC receptor (GR) is ubiquitous in carcinoma cells and has been linked to signal transduction pathways pertinent to cell growth and apoptosis, little is known regarding the possible effect of GC on the chemosensitivity of carcinomas. Our previous study demonstrated that dexamethasone (DEX) enhances the cytotoxicity to cisplatin in a GR-rich human cervical carcinoma cell line, SiHa. In this study, we found that this cisplatin cytotoxicity-enhancing effect of DEX correlated well with its effect on abrogating the cisplatin-induced activation of nuclear factor kappa B (NF-kappaB). RU486, a structural homologue of DEX, partially reversed this cytotoxicity-enhancing effect of DEX, a finding consistent with the well-known partial reversing effect of RU486 on DEX-induced NF-kappaB suppression. Furthermore, expression of a dominant-negative truncated IkappaBalpha gene in SiHa cells completely abolished the cisplatin cytotoxicity-enhancing effect of DEX. Our data suggest that the specific action of DEX on GR may enhance the cytotoxicity of cisplatin in selected GR-rich cancer cells by suppressing NF-kappaB activation. SN - 0022-0795 UR - https://www.unboundmedicine.com/medline/citation/16461557/Glucocorticoids_enhance_cytotoxicity_of_cisplatin_via_suppression_of_NF_{kappa}B_activation_in_the_glucocorticoid_receptor_rich_human_cervical_carcinoma_cell_line_SiHa_ L2 - https://joe.bioscientifica.com/doi/10.1677/joe.1.06453 DB - PRIME DP - Unbound Medicine ER -