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Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo.
Acta Biochim Biophys Sin (Shanghai). 2012 Oct; 44(10):847-55.AB

Abstract

Although constitutive activation of nuclear factor-kappaB (NF-κB) signaling pathway has been reported in multiple different human tumors, the role of NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. Abundant sources have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. In this study, we first analyzed the status of NF-κB pathway in the two ESCC cell lines Eca109 and EC9706, and then further investigated whether curcumin alone or in combination with 5-fluorouracil (5-FU) could modulate NF-κB pathway in vitro and in vivo. The results showed that NF-κB signaling pathway was constitutively activated in the ESCC cell lines. Curcumin suppressed the activation of NF-κB via the inhibition of IκBα phosphorylation, and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines. Curcumin combined with 5-FU led to the lower cell viability and higher apoptosis than 5-FU treated alone. In a human ESCC xenograft model, curcumin or 5-FU alone reduced the tumor volume, but their combination had the strongest anticancer effects. Besides, curcumin could also inhibit NF-κB signaling pathway through downregulation of the IκBα phosphorylation and induction of cell apoptosis in vivo. Overall, our results indicated that constitutively activated NF-κB signaling pathway exists in the two ESCC cells and the chemopreventive effects of curcumin were associated with downregulation of NF-κB signaling pathway and its downstream genes.

Authors+Show Affiliations

Department of Pathophysiology, School of Basic Medicine, Zhengzhou University, China. tianfang715@yahoo.com.cnNo 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

23017833

Citation

Tian, Fang, et al. "Curcumin Potentiates the Antitumor Effects of 5-FU in Treatment of Esophageal Squamous Carcinoma Cells Through Downregulating the Activation of NF-κB Signaling Pathway in Vitro and in Vivo." Acta Biochimica Et Biophysica Sinica, vol. 44, no. 10, 2012, pp. 847-55.
Tian F, Fan T, Zhang Y, et al. Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo. Acta Biochim Biophys Sin (Shanghai). 2012;44(10):847-55.
Tian, F., Fan, T., Zhang, Y., Jiang, Y., & Zhang, X. (2012). Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo. Acta Biochimica Et Biophysica Sinica, 44(10), 847-55.
Tian F, et al. Curcumin Potentiates the Antitumor Effects of 5-FU in Treatment of Esophageal Squamous Carcinoma Cells Through Downregulating the Activation of NF-κB Signaling Pathway in Vitro and in Vivo. Acta Biochim Biophys Sin (Shanghai). 2012;44(10):847-55. PubMed PMID: 23017833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo. AU - Tian,Fang, AU - Fan,Tianli, AU - Zhang,Yan, AU - Jiang,Yanan, AU - Zhang,Xiaoyan, PY - 2012/9/29/entrez PY - 2012/9/29/pubmed PY - 2013/2/28/medline SP - 847 EP - 55 JF - Acta biochimica et biophysica Sinica JO - Acta Biochim Biophys Sin (Shanghai) VL - 44 IS - 10 N2 - Although constitutive activation of nuclear factor-kappaB (NF-κB) signaling pathway has been reported in multiple different human tumors, the role of NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. Abundant sources have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. In this study, we first analyzed the status of NF-κB pathway in the two ESCC cell lines Eca109 and EC9706, and then further investigated whether curcumin alone or in combination with 5-fluorouracil (5-FU) could modulate NF-κB pathway in vitro and in vivo. The results showed that NF-κB signaling pathway was constitutively activated in the ESCC cell lines. Curcumin suppressed the activation of NF-κB via the inhibition of IκBα phosphorylation, and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines. Curcumin combined with 5-FU led to the lower cell viability and higher apoptosis than 5-FU treated alone. In a human ESCC xenograft model, curcumin or 5-FU alone reduced the tumor volume, but their combination had the strongest anticancer effects. Besides, curcumin could also inhibit NF-κB signaling pathway through downregulation of the IκBα phosphorylation and induction of cell apoptosis in vivo. Overall, our results indicated that constitutively activated NF-κB signaling pathway exists in the two ESCC cells and the chemopreventive effects of curcumin were associated with downregulation of NF-κB signaling pathway and its downstream genes. SN - 1745-7270 UR - https://www.unboundmedicine.com/medline/citation/23017833/Curcumin_potentiates_the_antitumor_effects_of_5_FU_in_treatment_of_esophageal_squamous_carcinoma_cells_through_downregulating_the_activation_of_NF_κB_signaling_pathway_in_vitro_and_in_vivo_ L2 - https://academic.oup.com/abbs/article-lookup/doi/10.1093/abbs/gms074 DB - PRIME DP - Unbound Medicine ER -