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Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets.
Cancer Lett. 2009 Jan 08; 273(1):86-97.CL

Abstract

Plant polyphenols possess anti-oxidant and anti-inflammatory activities and are hence potential candidates for preventing cancer. The present study was aimed at evaluating the anti-inflammatory and anti-tumor promoting activity of oligonol, a formulation of catechin-type oligomers, in mouse skin stimulated with a proto-type tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Pretreatment of mouse skin with oligonol significantly inhibited TPA-induced expression of cyclooxygenase-2 (COX-2). Oligonol diminished nuclear translocation and DNA binding of nuclear factor-kappaB (NF-kappaB) via blockade of phosphorylation and subsequent degradation of IkappaB alpha in TPA-treated mouse skin. Moreover, oligonol suppressed TPA-induced DNA binding of CCAAT/enhancer-binding protein (C/EBP) in mouse skin. Oligonol pretreatment also attenuated the phosphorylation and/or catalytic activities of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinase. Moreover, p38 MAP kinase inhibitor SB203580, but not the MEK inhibitor U0126, negated TPA-induced DNA binding of C/EBP. In addition, oligonol reduced the incidence and the multiplicity of papillomas and squamous cell carcinomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and TPA-promoted mouse skin, and prolonged the survival of tumor-bearing mice. Pretreatment with oligonol diminished the levels of proliferating cell nuclear antigen and expression of COX-2 in papillomas and carcinomas, respectively, as compared to DMBA plus TPA treatment alone. Taken together, the above findings suggest that oligonol inhibits TPA-induced COX-2 expression by blocking the activation of NF-kappaB and C/EBP via modulation of MAP kinases and suppresses chemically induced mouse skin tumorigenesis.

Authors+Show Affiliations

National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shillim-dong, Kwanak-ku, Seoul 151-742, Republic of Korea.No affiliation info availableNo affiliation info availableNo 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

18848748

Citation

Kundu, Joydeb Kumar, et al. "Inhibitory Effects of Oligonol On Phorbol Ester-induced Tumor Promotion and COX-2 Expression in Mouse Skin: NF-kappaB and C/EBP as Potential Targets." Cancer Letters, vol. 273, no. 1, 2009, pp. 86-97.
Kundu JK, Hwang DM, Lee JC, et al. Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets. Cancer Lett. 2009;273(1):86-97.
Kundu, J. K., Hwang, D. M., Lee, J. C., Chang, E. J., Shin, Y. K., Fujii, H., Sun, B., & Surh, Y. J. (2009). Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets. Cancer Letters, 273(1), 86-97. https://doi.org/10.1016/j.canlet.2008.07.039
Kundu JK, et al. Inhibitory Effects of Oligonol On Phorbol Ester-induced Tumor Promotion and COX-2 Expression in Mouse Skin: NF-kappaB and C/EBP as Potential Targets. Cancer Lett. 2009 Jan 8;273(1):86-97. PubMed PMID: 18848748.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets. AU - Kundu,Joydeb Kumar, AU - Hwang,Dal-Mi, AU - Lee,Jung-Chul, AU - Chang,Eun-Jin, AU - Shin,Young Kee, AU - Fujii,Hajime, AU - Sun,Buxiang, AU - Surh,Young-Joon, Y1 - 2008/10/10/ PY - 2008/03/15/received PY - 2008/05/15/revised PY - 2008/07/28/accepted PY - 2008/10/14/pubmed PY - 2009/1/6/medline PY - 2008/10/14/entrez SP - 86 EP - 97 JF - Cancer letters JO - Cancer Lett VL - 273 IS - 1 N2 - Plant polyphenols possess anti-oxidant and anti-inflammatory activities and are hence potential candidates for preventing cancer. The present study was aimed at evaluating the anti-inflammatory and anti-tumor promoting activity of oligonol, a formulation of catechin-type oligomers, in mouse skin stimulated with a proto-type tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Pretreatment of mouse skin with oligonol significantly inhibited TPA-induced expression of cyclooxygenase-2 (COX-2). Oligonol diminished nuclear translocation and DNA binding of nuclear factor-kappaB (NF-kappaB) via blockade of phosphorylation and subsequent degradation of IkappaB alpha in TPA-treated mouse skin. Moreover, oligonol suppressed TPA-induced DNA binding of CCAAT/enhancer-binding protein (C/EBP) in mouse skin. Oligonol pretreatment also attenuated the phosphorylation and/or catalytic activities of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinase. Moreover, p38 MAP kinase inhibitor SB203580, but not the MEK inhibitor U0126, negated TPA-induced DNA binding of C/EBP. In addition, oligonol reduced the incidence and the multiplicity of papillomas and squamous cell carcinomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and TPA-promoted mouse skin, and prolonged the survival of tumor-bearing mice. Pretreatment with oligonol diminished the levels of proliferating cell nuclear antigen and expression of COX-2 in papillomas and carcinomas, respectively, as compared to DMBA plus TPA treatment alone. Taken together, the above findings suggest that oligonol inhibits TPA-induced COX-2 expression by blocking the activation of NF-kappaB and C/EBP via modulation of MAP kinases and suppresses chemically induced mouse skin tumorigenesis. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/18848748/Inhibitory_effects_of_oligonol_on_phorbol_ester_induced_tumor_promotion_and_COX_2_expression_in_mouse_skin:_NF_kappaB_and_C/EBP_as_potential_targets_ DB - PRIME DP - Unbound Medicine ER -