Tags

Type your tag names separated by a space and hit enter

Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-kappa B.
Carcinogenesis. 2007 Jun; 28(6):1224-31.C

Abstract

Xanthorrhizol is an active component isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) that is traditionally used in Indonesia for medicinal purposes. In the present study, we found that the topical application of xanthorrhizol before 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment significantly inhibits TPA-induced mouse ear edema and TPA-induced tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated ICR mouse skin. The topical application of xanthorrhizol following the induction of papillomas with TPA-induced hyperplasia and dysplasia also reduced tumor multiplicity and incidence in DMBA-initiated mouse skin. To further elucidate the molecular mechanisms underlying the antitumor-promoting activity of xanthorrhizol, its effect on the TPA-induced expression of ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the upstream signaling molecules controlling these proteins were explored in mouse skin. The pre-treatment with xanthorrhizol inhibited the expression of ODC, iNOS and COX-2 proteins and nuclear factor-kappaB (NF-kappaB) activation in both mouse skin with TPA-induced acute inflammation and DMBA-initiated mouse skin promoted by TPA for 19 weeks. When mouse skin was treated after TPA-induced production of papillomas, xanthorrhizol remarkably suppressed the expression of ODC, iNOS and COX-2 and inhibited the activation of NF-kappaB. Furthermore, western blot analysis showed that xanthorrhizol suppressed the activation of extracellular signal-regulated protein kinase, p38, c-Jun-N-terminal kinase and Akt in mice after topical application for 6 weeks following the induction of papillomas. Taken together, the present study demonstrates that xanthorrhizol not only delays or inhibits tumor formation, but also reverses the carcinogenic process at pre-malignant stages by reducing the protein levels of ODC, iNOS and COX-2 regulated by the NF-kappaB, mitogen-activated protein kinases and/or Akt.

Authors+Show Affiliations

Department of Oral Biology, Yonsei University, College of Dentistry, Seodaemoon-Gu, Seoul, Korea.No 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

17234720

Citation

Chung, Won Yoon, et al. "Xanthorrhizol Inhibits 12-O-tetradecanoylphorbol-13-acetate-induced Acute Inflammation and Two-stage Mouse Skin Carcinogenesis By Blocking the Expression of Ornithine Decarboxylase, Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Through Mitogen-activated Protein Kinases And/or the Nuclear Factor-kappa B." Carcinogenesis, vol. 28, no. 6, 2007, pp. 1224-31.
Chung WY, Park JH, Kim MJ, et al. Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-kappa B. Carcinogenesis. 2007;28(6):1224-31.
Chung, W. Y., Park, J. H., Kim, M. J., Kim, H. O., Hwang, J. K., Lee, S. K., & Park, K. K. (2007). Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-kappa B. Carcinogenesis, 28(6), 1224-31.
Chung WY, et al. Xanthorrhizol Inhibits 12-O-tetradecanoylphorbol-13-acetate-induced Acute Inflammation and Two-stage Mouse Skin Carcinogenesis By Blocking the Expression of Ornithine Decarboxylase, Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Through Mitogen-activated Protein Kinases And/or the Nuclear Factor-kappa B. Carcinogenesis. 2007;28(6):1224-31. PubMed PMID: 17234720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor-kappa B. AU - Chung,Won Yoon, AU - Park,Jae Hee, AU - Kim,Mi Jeong, AU - Kim,Heui Ok, AU - Hwang,Jae Kwan, AU - Lee,Sang Kook, AU - Park,Kwang Kyun, Y1 - 2007/01/18/ PY - 2007/1/20/pubmed PY - 2007/8/8/medline PY - 2007/1/20/entrez SP - 1224 EP - 31 JF - Carcinogenesis JO - Carcinogenesis VL - 28 IS - 6 N2 - Xanthorrhizol is an active component isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) that is traditionally used in Indonesia for medicinal purposes. In the present study, we found that the topical application of xanthorrhizol before 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment significantly inhibits TPA-induced mouse ear edema and TPA-induced tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated ICR mouse skin. The topical application of xanthorrhizol following the induction of papillomas with TPA-induced hyperplasia and dysplasia also reduced tumor multiplicity and incidence in DMBA-initiated mouse skin. To further elucidate the molecular mechanisms underlying the antitumor-promoting activity of xanthorrhizol, its effect on the TPA-induced expression of ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the upstream signaling molecules controlling these proteins were explored in mouse skin. The pre-treatment with xanthorrhizol inhibited the expression of ODC, iNOS and COX-2 proteins and nuclear factor-kappaB (NF-kappaB) activation in both mouse skin with TPA-induced acute inflammation and DMBA-initiated mouse skin promoted by TPA for 19 weeks. When mouse skin was treated after TPA-induced production of papillomas, xanthorrhizol remarkably suppressed the expression of ODC, iNOS and COX-2 and inhibited the activation of NF-kappaB. Furthermore, western blot analysis showed that xanthorrhizol suppressed the activation of extracellular signal-regulated protein kinase, p38, c-Jun-N-terminal kinase and Akt in mice after topical application for 6 weeks following the induction of papillomas. Taken together, the present study demonstrates that xanthorrhizol not only delays or inhibits tumor formation, but also reverses the carcinogenic process at pre-malignant stages by reducing the protein levels of ODC, iNOS and COX-2 regulated by the NF-kappaB, mitogen-activated protein kinases and/or Akt. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/17234720/Xanthorrhizol_inhibits_12_O_tetradecanoylphorbol_13_acetate_induced_acute_inflammation_and_two_stage_mouse_skin_carcinogenesis_by_blocking_the_expression_of_ornithine_decarboxylase_cyclooxygenase_2_and_inducible_nitric_oxide_synthase_through_mitogen_activated_protein_kinases_and/or_the_nuclear_factor_kappa_B_ DB - PRIME DP - Unbound Medicine ER -