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Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells
Pooja Chandrakant Thacker,
Published in Public Library of Science
2015
PMID: 25786122
Volume: 10
   
Issue: 3
Abstract
Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer. © 2015 Thacker, Karunagaran.
About the journal
JournalPLoS ONE
PublisherPublic Library of Science
ISSN19326203
Open AccessYes
Concepts (92)
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    Beta catenin
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    Curcumin
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    Cyclin d1
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    Emodin
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    PEPTIDYLPROLYL ISOMERASE PIN1
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    Protein p21
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    SMAD3 PROTEIN
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    SMAD4 PROTEIN
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    TRANSCRIPTION FACTOR SLUG
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    TRANSCRIPTION FACTOR SNAIL
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    TRANSFORMING GROWTH FACTOR BETA
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    TRANSFORMING GROWTH FACTOR BETA RECEPTOR 2
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    WNT PROTEIN
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    Antineoplastic agent
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    CCND1 PROTEIN, HUMAN
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    Collagen
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    CTNNB1 PROTEIN, HUMAN
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    Cyclin dependent kinase inhibitor 1a
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    DRUG COMBINATION
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    LAMININ
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    MATRIGEL
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    NIMA INTERACTING PEPTIDYLPROLYL ISOMERASE
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    PEPTIDYLPROLYL ISOMERASE
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    PIN1 PROTEIN, HUMAN
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    Protein serine threonine kinase
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    Proteoglycan
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    SMAD3 PROTEIN
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    SMAD3 PROTEIN, HUMAN
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    SMAD4 PROTEIN
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    SMAD4 PROTEIN, HUMAN
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    SNAI1 PROTEIN, HUMAN
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    Transcription factor
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    TRANSCRIPTION FACTOR SNAIL
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    TRANSFORMING GROWTH FACTOR BETA
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    TRANSFORMING GROWTH FACTOR BETA RECEPTOR
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    TRANSFORMING GROWTH FACTOR-BETA TYPE II RECEPTOR
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    WNT PROTEIN
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    Antineoplastic activity
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    Article
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    Cell growth
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    Cell invasion
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    Cell migration
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    Cell viability
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    CERVICAL CANCER CELL LINE
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    Concentration response
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    Controlled study
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    Cytotoxicity
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    Drug mechanism
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    Drug potentiation
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    Female
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    Human
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    Human cell
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    Mitochondrial membrane potential
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    Mitosis inhibition
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    Protein expression
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    Signal transduction
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    Antagonists and inhibitors
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    Cell motion
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    Cell proliferation
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    Chemistry
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    DRUG COMBINATION
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    Drug effects
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    Epithelial mesenchymal transition
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    Gene expression regulation
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    Genetics
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    Hela cell line
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    Metabolism
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    Tumor cell line
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    Gastropoda
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    HUMAN PAPILLOMAVIRUS
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    Antineoplastic agents, phytogenic
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    Cell line, tumor
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    Cell movement
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    Cyclin-dependent kinase inhibitor p21
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    Drug combinations
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    Drug synergism
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    Epithelial-mesenchymal transition
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    GENE EXPRESSION REGULATION, NEOPLASTIC
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    Hela cells
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    Humans
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    LAMININ
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    NIMA-INTERACTING PEPTIDYLPROLYL ISOMERASE
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    PEPTIDYLPROLYL ISOMERASE
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    Protein-serine-threonine kinases
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    Proteoglycans
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    RECEPTORS, TRANSFORMING GROWTH FACTOR BETA
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    SMAD3 PROTEIN
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    SMAD4 PROTEIN
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    SNAIL FAMILY TRANSCRIPTION FACTORS
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    Transcription factors
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    TRANSFORMING GROWTH FACTOR BETA
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    WNT PROTEINS