Skip to main content
Top
Published in: Annals of Surgical Oncology 11/2012

01-10-2012 | Hepatobiliary Tumors

Knockdown Survivin Expression Reduces the Efficacy of Curcumin Treatment in Hepatocellular Carcinoma Cells

Authors: Chin-Sheng Hung, MD, Hui-Hsiung Liu, MD, PhD, Ming-Te Huang, MD, Chao-Wen Cheng, PhD, Li-Jen Kuo, MD, Yuan-Soon Ho, PhD, Chih-Hsiung Wu, MD, PhD, Chien-Ming Chen, MS, Po-Li Wei, MD, PhD, Yu-Jia Chang, PhD

Published in: Annals of Surgical Oncology | Issue 11/2012

Login to get access

Abstract

Background

Survivin is a potential therapeutic target for cancer. Increased survivin expression promotes cell survival and therapeutic resistance. However, there is little information regarding whether the expression level of survivin affects curcumin treatment in hepatocellular carcinoma (HCC).

Methods

Survivin expression was suppressed in HCC cells using a short interfering RNA (siRNA) technique. The anticancer effects of curcumin were examined using a biosensor system, MTT assay, TUNEL assay, and cell cycle analysis.

Results

Curcumin resistance developed in cells with suppressed survivin, in contrast to the parental cells, as determined by survival assays. Cell cycle analysis and TUNEL assays revealed that the apoptotic cell population was increased in the scrambled-siRNA cells treated with curcumin compared with the survivin-siRNA cells. Suppression of survivin expression resulted in curcumin resistance via the modulation of Bcl-2 and Bax expression.

Conclusions

We conclude that the expression levels of survivin may mediate the therapeutic efficacy of curcumin in HCC cells.
Literature
1.
go back to reference Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–9.PubMedCrossRef Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–9.PubMedCrossRef
3.
go back to reference Thomas MB, Zhu AX. Hepatocellular carcinoma: the need for progress. J Clin Oncol. 2005;23:2892–9.PubMedCrossRef Thomas MB, Zhu AX. Hepatocellular carcinoma: the need for progress. J Clin Oncol. 2005;23:2892–9.PubMedCrossRef
4.
5.
go back to reference Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21.PubMedCrossRef Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21.PubMedCrossRef
7.
go back to reference Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998;396:580–4.PubMedCrossRef Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998;396:580–4.PubMedCrossRef
8.
go back to reference Chandele A, Prasad V, Jagtap JC, Shukla R, Shastry PR. Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis. Neoplasia. 2004;6:29–40.PubMed Chandele A, Prasad V, Jagtap JC, Shukla R, Shastry PR. Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis. Neoplasia. 2004;6:29–40.PubMed
9.
go back to reference Fields AC, Cotsonis G, Sexton D, Santoianni R, Cohen C. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol. 2004;17:1378–85.PubMedCrossRef Fields AC, Cotsonis G, Sexton D, Santoianni R, Cohen C. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol. 2004;17:1378–85.PubMedCrossRef
10.
go back to reference Augello C, Caruso L, Maggioni M, Donadon M, Montorsi M, Santambrogio R, et al. Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma. BMC Cancer. 2009;9:125.PubMedCrossRef Augello C, Caruso L, Maggioni M, Donadon M, Montorsi M, Santambrogio R, et al. Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma. BMC Cancer. 2009;9:125.PubMedCrossRef
11.
go back to reference Huang MT, Wei PL, Liu JJ, Liu DZ, Huey-Chun H, An J, et al. Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. Ann Surg Oncol. 2010;17:3379–85.PubMedCrossRef Huang MT, Wei PL, Liu JJ, Liu DZ, Huey-Chun H, An J, et al. Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. Ann Surg Oncol. 2010;17:3379–85.PubMedCrossRef
12.
go back to reference Zhang T, Ding X, Wei D, Cheng P, Su X, Liu H, et al. Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials. Anticancer Drugs. 2010;21:326–32.PubMedCrossRef Zhang T, Ding X, Wei D, Cheng P, Su X, Liu H, et al. Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials. Anticancer Drugs. 2010;21:326–32.PubMedCrossRef
13.
go back to reference Aoki Y, Feldman GM, Tosato G. Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood. 2003;101:1535–42.PubMedCrossRef Aoki Y, Feldman GM, Tosato G. Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood. 2003;101:1535–42.PubMedCrossRef
14.
go back to reference Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 2004;23:4921–9.PubMedCrossRef Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 2004;23:4921–9.PubMedCrossRef
15.
go back to reference Fuke H, Shiraki K, Sugimoto K, Tanaka J, Beppu T, Yoneda K, et al. Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2007;363:738–44.PubMedCrossRef Fuke H, Shiraki K, Sugimoto K, Tanaka J, Beppu T, Yoneda K, et al. Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2007;363:738–44.PubMedCrossRef
16.
go back to reference Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett. 2008;267:133–64.PubMedCrossRef Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett. 2008;267:133–64.PubMedCrossRef
17.
go back to reference Shishodia S, Singh T, Chaturvedi MM. Modulation of transcription factors by curcumin. Adv Exp Med Biol. 2007;595:127–48.PubMedCrossRef Shishodia S, Singh T, Chaturvedi MM. Modulation of transcription factors by curcumin. Adv Exp Med Biol. 2007;595:127–48.PubMedCrossRef
18.
go back to reference Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11:495–510.PubMedCrossRef Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11:495–510.PubMedCrossRef
19.
go back to reference Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007;255:170–81.PubMedCrossRef Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007;255:170–81.PubMedCrossRef
20.
go back to reference Glienke W, Maute L, Wicht J, Bergmann L. Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression. Cancer Invest. 2010;28:166–71.PubMedCrossRef Glienke W, Maute L, Wicht J, Bergmann L. Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression. Cancer Invest. 2010;28:166–71.PubMedCrossRef
21.
go back to reference Chang YJ, Tai CJ, Kuo LJ, Wei PL, Liang HH, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) mediated the efficacy to curcumin treatment on hepatocellular carcinoma. Ann Surg Oncol. 2011;18:2395–403.PubMedCrossRef Chang YJ, Tai CJ, Kuo LJ, Wei PL, Liang HH, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) mediated the efficacy to curcumin treatment on hepatocellular carcinoma. Ann Surg Oncol. 2011;18:2395–403.PubMedCrossRef
22.
go back to reference Chang YJ, Chiu CC, Wu CH, An J, Wu CC, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) silencing enhances cell migration but does not influence cell proliferation in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:1703–9.PubMedCrossRef Chang YJ, Chiu CC, Wu CH, An J, Wu CC, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) silencing enhances cell migration but does not influence cell proliferation in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:1703–9.PubMedCrossRef
23.
go back to reference Chiou JF, Tai CJ, Huang MT, Wei PL, Wang YH, An J, et al. Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:603–12.PubMedCrossRef Chiou JF, Tai CJ, Huang MT, Wei PL, Wang YH, An J, et al. Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:603–12.PubMedCrossRef
24.
go back to reference Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef
25.
go back to reference Wang SK, Liang PH, Astronomo RD, Hsu TL, Hsieh SL, Burton DR, et al. Targeting the carbohydrates on HIV-1: interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc Natl Acad Sci USA. 2008;105:3690–5.PubMedCrossRef Wang SK, Liang PH, Astronomo RD, Hsu TL, Hsieh SL, Burton DR, et al. Targeting the carbohydrates on HIV-1: interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc Natl Acad Sci USA. 2008;105:3690–5.PubMedCrossRef
26.
go back to reference Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Köhler K, et al. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol. 2008;10:211–9.PubMedCrossRef Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Köhler K, et al. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol. 2008;10:211–9.PubMedCrossRef
27.
go back to reference Monzo M, Rosell R, Felip E, Astudillo J, Sánchez JJ, Maestre J, et al. A novel anti-apoptosis gene: re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J Clin Oncol. 1999;17:2100–4.PubMed Monzo M, Rosell R, Felip E, Astudillo J, Sánchez JJ, Maestre J, et al. A novel anti-apoptosis gene: re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J Clin Oncol. 1999;17:2100–4.PubMed
28.
go back to reference Satoh K, Kaneko K, Hirota M, Masamune A, Satoh A, Shimosegawa T. Tumor necrosis factor-related apoptosis-inducing ligand and its receptor expression and the pathway of apoptosis in human pancreatic cancer. Pancreas. 2001;23:251–8.PubMedCrossRef Satoh K, Kaneko K, Hirota M, Masamune A, Satoh A, Shimosegawa T. Tumor necrosis factor-related apoptosis-inducing ligand and its receptor expression and the pathway of apoptosis in human pancreatic cancer. Pancreas. 2001;23:251–8.PubMedCrossRef
29.
go back to reference Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 1998;58:5071–4.PubMed Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 1998;58:5071–4.PubMed
30.
go back to reference Tai CJ, Chin-Sheng H, Kuo LJ, Wei PL, Lu HH, Chen HA, et al. Survivin-mediated cancer cell migration through GRP78 and epithelial-mesenchymal transition (EMT) marker expression in Mahlavu cells. Ann Surg Oncol. 2012;19:336–43.PubMedCrossRef Tai CJ, Chin-Sheng H, Kuo LJ, Wei PL, Lu HH, Chen HA, et al. Survivin-mediated cancer cell migration through GRP78 and epithelial-mesenchymal transition (EMT) marker expression in Mahlavu cells. Ann Surg Oncol. 2012;19:336–43.PubMedCrossRef
31.
go back to reference Watson JL, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, et al. Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog. 2010;49:13–24.PubMed Watson JL, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, et al. Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog. 2010;49:13–24.PubMed
32.
go back to reference Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091–6.PubMedCrossRef Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091–6.PubMedCrossRef
33.
go back to reference Dean-Colomb W, Esteva FJ. Her2-positive breast cancer: herceptin and beyond. Eur J Cancer. 2008;44:2806–12.PubMedCrossRef Dean-Colomb W, Esteva FJ. Her2-positive breast cancer: herceptin and beyond. Eur J Cancer. 2008;44:2806–12.PubMedCrossRef
Metadata
Title
Knockdown Survivin Expression Reduces the Efficacy of Curcumin Treatment in Hepatocellular Carcinoma Cells
Authors
Chin-Sheng Hung, MD
Hui-Hsiung Liu, MD, PhD
Ming-Te Huang, MD
Chao-Wen Cheng, PhD
Li-Jen Kuo, MD
Yuan-Soon Ho, PhD
Chih-Hsiung Wu, MD, PhD
Chien-Ming Chen, MS
Po-Li Wei, MD, PhD
Yu-Jia Chang, PhD
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 11/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2393-4

Other articles of this Issue 11/2012

Annals of Surgical Oncology 11/2012 Go to the issue

Hepatobiliary Tumors

Upper Transversal Hepatectomy