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Erschienen in: Journal of Cancer Research and Clinical Oncology 4/2013

01.04.2013 | Original Paper

Role of TGF-β signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells

verfasst von: Raktima Datta, Sunil K. Halder, Binhao Zhang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2013

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Abstract

Purpose

Curcumin has been shown to have potent anticancer activities like inhibition of cell proliferation, induction of apoptosis, and suppression of angiogenesis. Transforming growth factor-β (TGF-β) signaling plays a complex role in tumor suppression and promotion depending on the tumor type and stage. However, the effect of curcumin on TGF-β signaling in cancer cells and the role of TGF-β signaling in curcumin-induced anticancer activities have not been determined. Here, we investigate the role of curcumin on TGF-β signaling, and whether TGF-β signaling is involved in the antitumor activities of curcumin.

Methods

Human non-small cell lung cancer (NSCLC) cell lines, ACC-LC-176 (without TGF-β signaling), H358, and A549 (with TGF-β signaling) were treated with curcumin to determine cell growth, apoptosis, and tumorigenicity. Antitumor activities of curcumin were determined using these cell lines and an in vivo mouse model. We also tested the effect of curcumin on TGF-β/Smad signaling by western blotting and by luciferase assays.

Results

Curcumin inhibited cell growth and induced apoptosis of all three NSCLC cell lines in vitro and in vivo. It significantly reduced subcutaneous tumor growth by these three cell lines irrespective of TGF-β signaling status. Curcumin inhibited TGF-β-induced Smad2/3 phosphorylation and transcription in H358 and A549 cells, but not in ACC-LC-176 cells.

Conclusions

Curcumin reduces tumorigenicity of human lung cancer cells in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. These results suggest that TGF-β signaling is not directly involved in curcumin-mediated growth inhibition, induction of apoptosis, and inhibition of tumorigenicity.
Literatur
Zurück zum Zitat Anumanthan G, Halder SK, Osada H, Takahashi T, Massion PP, Carbone DP, Datta PK (2005) Restoration of TGF-beta signalling reduces tumorigenicity in human lung cancer cells. Br J Cancer 93(10):1157–1167PubMedCrossRef Anumanthan G, Halder SK, Osada H, Takahashi T, Massion PP, Carbone DP, Datta PK (2005) Restoration of TGF-beta signalling reduces tumorigenicity in human lung cancer cells. Br J Cancer 93(10):1157–1167PubMedCrossRef
Zurück zum Zitat Bayet-Robert M, Kwiatkowski F, Leheurteur M, Gachon F, Planchat E, Abrial C, Mouret-Reynier MA, Durando X, Barthomeuf C, Chollet P (2010) Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 9(1):8–14PubMedCrossRef Bayet-Robert M, Kwiatkowski F, Leheurteur M, Gachon F, Planchat E, Abrial C, Mouret-Reynier MA, Durando X, Barthomeuf C, Chollet P (2010) Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther 9(1):8–14PubMedCrossRef
Zurück zum Zitat Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, Kakarala M, Carpenter PM, McLaren C, Meyskens FL Jr, Brenner DE (2011) Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 4(3):354–364CrossRef Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, Kakarala M, Carpenter PM, McLaren C, Meyskens FL Jr, Brenner DE (2011) Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 4(3):354–364CrossRef
Zurück zum Zitat Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4B):2895–2900PubMed Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4B):2895–2900PubMed
Zurück zum Zitat Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584PubMedCrossRef Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584PubMedCrossRef
Zurück zum Zitat Gaedeke J, Noble NA, Border WA (2004) Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells. Kidney Int 66(1):112–120PubMedCrossRef Gaedeke J, Noble NA, Border WA (2004) Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells. Kidney Int 66(1):112–120PubMedCrossRef
Zurück zum Zitat Halder SK, Beauchamp RD, Datta PK (2005) Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res 307(1):231–246PubMedCrossRef Halder SK, Beauchamp RD, Datta PK (2005) Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res 307(1):231–246PubMedCrossRef
Zurück zum Zitat Halder SK, Cho YJ, Datta A, Anumanthan G, Ham AJ, Carbone DP, Datta PK (2011) Elucidating the mechanism of regulation of transforming growth factor beta type II receptor expression in human lung cancer cell lines. Neoplasia 13(10):912–922PubMed Halder SK, Cho YJ, Datta A, Anumanthan G, Ham AJ, Carbone DP, Datta PK (2011) Elucidating the mechanism of regulation of transforming growth factor beta type II receptor expression in human lung cancer cell lines. Neoplasia 13(10):912–922PubMed
Zurück zum Zitat Hsu YC, Chen MJ, Yu YM, Ko SY, Chang CC (2010) Suppression of TGF-beta1/SMAD pathway and extracellular matrix production in primary keloid fibroblasts by curcuminoids: its potential therapeutic use in the chemoprevention of keloid. Arch Dermatol Res 302(10):717–724PubMedCrossRef Hsu YC, Chen MJ, Yu YM, Ko SY, Chang CC (2010) Suppression of TGF-beta1/SMAD pathway and extracellular matrix production in primary keloid fibroblasts by curcuminoids: its potential therapeutic use in the chemoprevention of keloid. Arch Dermatol Res 302(10):717–724PubMedCrossRef
Zurück zum Zitat Kim SY, Jung SH, Kim HS (2005) Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun 337(2):510–516PubMedCrossRef Kim SY, Jung SH, Kim HS (2005) Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun 337(2):510–516PubMedCrossRef
Zurück zum Zitat Lin SS, Lai KC, Hsu SC, Yang JS, Kuo CL, Lin JP, Ma YS, Wu CC, Chung JG (2009) Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor (VEGF). Cancer Lett 285(2):127–133PubMedCrossRef Lin SS, Lai KC, Hsu SC, Yang JS, Kuo CL, Lin JP, Ma YS, Wu CC, Chung JG (2009) Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor (VEGF). Cancer Lett 285(2):127–133PubMedCrossRef
Zurück zum Zitat Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E (2004) Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett 208(2):163–170PubMedCrossRef Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E (2004) Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett 208(2):163–170PubMedCrossRef
Zurück zum Zitat Sakurai R, Li Y, Torday JS, Rehan VK (2011) Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-beta signaling. Am J Physiol Lung Cell Mol Physiol 301(5):L721–L730PubMedCrossRef Sakurai R, Li Y, Torday JS, Rehan VK (2011) Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-beta signaling. Am J Physiol Lung Cell Mol Physiol 301(5):L721–L730PubMedCrossRef
Zurück zum Zitat Samaha HS, Kelloff GJ, Steele V, Rao CV, Reddy BS (1997) Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcaffeate, and 6-phenylhexyl isothiocyanate: apoptotic index as a biomarker in colon cancer chemoprevention and promotion. Cancer Res 57(7):1301–1305PubMed Samaha HS, Kelloff GJ, Steele V, Rao CV, Reddy BS (1997) Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcaffeate, and 6-phenylhexyl isothiocyanate: apoptotic index as a biomarker in colon cancer chemoprevention and promotion. Cancer Res 57(7):1301–1305PubMed
Zurück zum Zitat Samanta D, Gonzalez AL, Nagathihalli N, Ye F, Carbone DP, Datta PK (2012) Smoking attenuates transforming growth factor-beta-mediated tumor suppression function through downregulation of Smad3 in lung cancer. Cancer Prev Res (Phila) 5(3):453–463CrossRef Samanta D, Gonzalez AL, Nagathihalli N, Ye F, Carbone DP, Datta PK (2012) Smoking attenuates transforming growth factor-beta-mediated tumor suppression function through downregulation of Smad3 in lung cancer. Cancer Prev Res (Phila) 5(3):453–463CrossRef
Zurück zum Zitat Shishodia S, Chaturvedi MM, Aggarwal BB (2007) Role of curcumin in cancer therapy. Curr Probl Cancer 31(4):243–305PubMedCrossRef Shishodia S, Chaturvedi MM, Aggarwal BB (2007) Role of curcumin in cancer therapy. Curr Probl Cancer 31(4):243–305PubMedCrossRef
Zurück zum Zitat Song K, Peng S, Sun Z, Li H, Yang R (2011) Curcumin suppresses TGF-beta signaling by inhibition of TGIF degradation in scleroderma fibroblasts. Biochem Biophys Res Commun 411(4):821–825PubMedCrossRef Song K, Peng S, Sun Z, Li H, Yang R (2011) Curcumin suppresses TGF-beta signaling by inhibition of TGIF degradation in scleroderma fibroblasts. Biochem Biophys Res Commun 411(4):821–825PubMedCrossRef
Zurück zum Zitat Su CC, Yang JS, Lu CC, Chiang JH, Wu CL, Lin JJ, Lai KC, Hsia TC, Lu HF, Fan MJ, Chung JG (2010) Curcumin inhibits human lung large cell carcinoma cancer tumour growth in a murine xenograft model. Phytother Res 24(2):189–192PubMed Su CC, Yang JS, Lu CC, Chiang JH, Wu CL, Lin JJ, Lai KC, Hsia TC, Lu HF, Fan MJ, Chung JG (2010) Curcumin inhibits human lung large cell carcinoma cancer tumour growth in a murine xenograft model. Phytother Res 24(2):189–192PubMed
Zurück zum Zitat Thangapazham RL, Sharma A, Maheshwari RK (2006) Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J 8(3):E443–E449PubMedCrossRef Thangapazham RL, Sharma A, Maheshwari RK (2006) Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J 8(3):E443–E449PubMedCrossRef
Zurück zum Zitat Yang CL, Liu YY, Ma YG, Xue YX, Liu DG, Ren Y, Liu XB, Li Y, Li Z (2012a) Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS ONE 7(5):e37960PubMedCrossRef Yang CL, Liu YY, Ma YG, Xue YX, Liu DG, Ren Y, Liu XB, Li Y, Li Z (2012a) Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS ONE 7(5):e37960PubMedCrossRef
Zurück zum Zitat Yang CW, Chang CL, Lee HC, Chi CW, Pan JP, Yang WC (2012b) Curcumin induces the apoptosis of human monocytic leukemia THP-1 cells via the activation of JNK/ERK pathways. BMC Complement Altern Med 12:22PubMedCrossRef Yang CW, Chang CL, Lee HC, Chi CW, Pan JP, Yang WC (2012b) Curcumin induces the apoptosis of human monocytic leukemia THP-1 cells via the activation of JNK/ERK pathways. BMC Complement Altern Med 12:22PubMedCrossRef
Metadaten
Titel
Role of TGF-β signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells
verfasst von
Raktima Datta
Sunil K. Halder
Binhao Zhang
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-012-1352-6

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