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Title: Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin

Abstract

Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-{kappa}B), we also investigated the effect of bromelain on Cox-2 and NF-{kappa}B expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-{kappa}B by blocking phosphorylation and subsequent degradation of I{kappa}B{alpha}. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition ofmore » NF-{kappa}B-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects.« less

Authors:
; ; ; ; ;  [1];  [2]
  1. Proteomics Laboratory, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001 (India)
  2. Proteomics Laboratory, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001 (India), E-mail: yogeshwer_shukla@hotmail.com
Publication Date:
OSTI Identifier:
21077884
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 226; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.08.012; PII: S0041-008X(07)00375-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; ANTHRACENE; APOPTOSIS; DIMETHYLBENZANTHRACENE; INFLAMMATION; METASTASES; MICE; NEOPLASMS; OXYGEN 12; PHOSPHORYLATION; PINEAPPLES; PROTEINS; SKIN

Citation Formats

Kalra, Neetu, Bhui, Kulpreet, Roy, Preeti, Srivastava, Smita, George, Jasmine, Prasad, Sahdeo, and Shukla, Yogeshwer. Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.08.012.
Kalra, Neetu, Bhui, Kulpreet, Roy, Preeti, Srivastava, Smita, George, Jasmine, Prasad, Sahdeo, & Shukla, Yogeshwer. Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. United States. doi:10.1016/j.taap.2007.08.012.
Kalra, Neetu, Bhui, Kulpreet, Roy, Preeti, Srivastava, Smita, George, Jasmine, Prasad, Sahdeo, and Shukla, Yogeshwer. Tue . "Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin". United States. doi:10.1016/j.taap.2007.08.012.
@article{osti_21077884,
title = {Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin},
author = {Kalra, Neetu and Bhui, Kulpreet and Roy, Preeti and Srivastava, Smita and George, Jasmine and Prasad, Sahdeo and Shukla, Yogeshwer},
abstractNote = {Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-{kappa}B), we also investigated the effect of bromelain on Cox-2 and NF-{kappa}B expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-{kappa}B by blocking phosphorylation and subsequent degradation of I{kappa}B{alpha}. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition of NF-{kappa}B-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects.},
doi = {10.1016/j.taap.2007.08.012},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 226,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 2008},
month = {Tue Jan 01 00:00:00 EST 2008}
}