Skip to main content
Top
Published in: Annals of Surgical Oncology 8/2011

01-08-2011 | Translational Research and Biomarkers

Glucose-Regulated Protein 78 (GRP78) Mediated the Efficacy to Curcumin Treatment on Hepatocellular Carcinoma

Authors: Yu-Jia Chang, PhD, Cheng-Jeng Tai, MD, Li-Jen Kuo, MD, Po-Li Wei, MD, PhD, Hung-Hua Liang, MD, Tsan-Zon Liu, PhD, Weu Wang, MD, Chen-Jei Tai, MD, PhD, Yuan-Soon Ho, PhD, Chih-Hsiung Wu, MD, PhD, Ming-Te Huang, MD

Published in: Annals of Surgical Oncology | Issue 8/2011

Login to get access

Abstract

Background

Glucose-regulated protein 78 (GRP78) plays an important role in the therapeutic treatment and progression of cancer. However, little is known about the effect of GRP78 expression to curcumin in hepatocellular carcinoma (HCC).

Materials and Methods

In this study, we generated GRP78 knockdown cells (GRP78KD) by a short interfering RNA (siRNA) technique. The antiproliferation effects of curcumin were determined by MTT assay, TUNEL assay, and cell cycle determination.

Results

We found that GRP78KD cells were more resistant to curcumin treatment compared with the parental cells in MTT assay. The apoptosis cell population was increased in scrambled-siRNA cells treated with curcumin compared with GRP78KD cells in cell cycle distribution and TUNEL assays. Finally, we found that knocking down GRP78 causes resistance to curcumin treatment through the suppression of caspase-3 and caspase-8 expression levels.

Conclusions

We conclude that the expression level of GRP78 may contribute to the therapeutic effect of curcumin on HCC cells.
Literature
2.
go back to reference Cabrera R, Nelson DR. Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther. 2010;31:461–76.PubMedCrossRef Cabrera R, Nelson DR. Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther. 2010;31:461–76.PubMedCrossRef
3.
go back to reference Nagorney DM, van Heerden JA, Ilstrup DM, Adson MA. Primary hepatic malignancy: surgical management and determinants of survival. Surgery 1989;106:740–8 (discussion 748–9).PubMed Nagorney DM, van Heerden JA, Ilstrup DM, Adson MA. Primary hepatic malignancy: surgical management and determinants of survival. Surgery 1989;106:740–8 (discussion 748–9).PubMed
4.
go back to reference Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Liver Cancer Study Group of Japan. Ann Surg 1990;211:277–87. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Liver Cancer Study Group of Japan. Ann Surg 1990;211:277–87.
5.
go back to reference Paquet KJ, Koussouris P, Mercado MA, Kalk JF, Müting D, Rambach W. Limited hepatic resection for selected cirrhotic patients with hepatocellular or cholangiocellular carcinoma: a prospective study. Br J Surg. 1991;78:459–62.PubMedCrossRef Paquet KJ, Koussouris P, Mercado MA, Kalk JF, Müting D, Rambach W. Limited hepatic resection for selected cirrhotic patients with hepatocellular or cholangiocellular carcinoma: a prospective study. Br J Surg. 1991;78:459–62.PubMedCrossRef
6.
go back to reference Sugioka A, Tsuzuki T, Kanai T. Postresection prognosis of patients with hepatocellular carcinoma. Surgery. 1993;113:612–8.PubMed Sugioka A, Tsuzuki T, Kanai T. Postresection prognosis of patients with hepatocellular carcinoma. Surgery. 1993;113:612–8.PubMed
7.
go back to reference Huang CC, Wu MC, Xu GW, Li DZ, Cheng H, Tu ZX, et al. Overexpression of the MDR1 gene and P-glycoprotein in human hepatocellular carcinoma. J Natl Cancer Inst. 1992;84:262–4.PubMedCrossRef Huang CC, Wu MC, Xu GW, Li DZ, Cheng H, Tu ZX, et al. Overexpression of the MDR1 gene and P-glycoprotein in human hepatocellular carcinoma. J Natl Cancer Inst. 1992;84:262–4.PubMedCrossRef
8.
go back to reference Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66:11851–8.PubMedCrossRef Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66:11851–8.PubMedCrossRef
9.
go back to reference Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef
10.
go back to reference Cheng AL, Kang YK, Chen Z, Tsao J, 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 J, 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
11.
go back to reference Rimassa L, Santoro A. Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial. Expert Rev Anticancer Ther. 2009;9:739–45.PubMedCrossRef Rimassa L, Santoro A. Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial. Expert Rev Anticancer Ther. 2009;9:739–45.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 Vitale A, Volk ML, Pastorelli D, Lonardi S, Farinati F, Burra P, et al. Use of sorafenib in patients with hepatocellular carcinoma before liver transplantation: a cost-benefit analysis while awaiting data on sorafenib safety. Hepatology. 2010;51:165–73.PubMed Vitale A, Volk ML, Pastorelli D, Lonardi S, Farinati F, Burra P, et al. Use of sorafenib in patients with hepatocellular carcinoma before liver transplantation: a cost-benefit analysis while awaiting data on sorafenib safety. Hepatology. 2010;51:165–73.PubMed
14.
go back to reference A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28:751–5. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28:751–5.
15.
go back to reference Hsu C, Shen YC, Cheng CC, Hu FC, Cheng AL. Geographic difference in survival outcome for advanced hepatocellular carcinoma: implications on future clinical trial design. Contemp Clin Trials. 2010;31:55–61.PubMedCrossRef Hsu C, Shen YC, Cheng CC, Hu FC, Cheng AL. Geographic difference in survival outcome for advanced hepatocellular carcinoma: implications on future clinical trial design. Contemp Clin Trials. 2010;31:55–61.PubMedCrossRef
16.
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
17.
go back to reference Lim SO, Park SG, Yoo JH, Park YM, Kim HJ, Jang KT, et al. Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules. World J Gastroenterol. 2005;11:2072–9.PubMed Lim SO, Park SG, Yoo JH, Park YM, Kim HJ, Jang KT, et al. Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules. World J Gastroenterol. 2005;11:2072–9.PubMed
18.
go back to reference Luk JM, Lam CT, Siu AF, Lam BY, Ng IO, Hu MY, et al. Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values. Proteomics. 2006;6:1049–57.PubMedCrossRef Luk JM, Lam CT, Siu AF, Lam BY, Ng IO, Hu MY, et al. Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values. Proteomics. 2006;6:1049–57.PubMedCrossRef
19.
go back to reference Shuda M, Kondoh N, Imazeki N, Tanaka K, Okada T, Mori K, et al. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol. 2003;38:605–14.PubMedCrossRef Shuda M, Kondoh N, Imazeki N, Tanaka K, Okada T, Mori K, et al. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol. 2003;38:605–14.PubMedCrossRef
20.
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
22.
go back to reference Singh S, Khar A. Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anticancer Agents Med Chem. 2006;6:259–70.PubMedCrossRef Singh S, Khar A. Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anticancer Agents Med Chem. 2006;6:259–70.PubMedCrossRef
23.
go back to reference Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem. 2007;102:522–38.PubMedCrossRef Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem. 2007;102:522–38.PubMedCrossRef
24.
go back to reference Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269:199–225.PubMedCrossRef Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269:199–225.PubMedCrossRef
25.
go back to reference Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 2006;71:1397–421.PubMedCrossRef Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 2006;71:1397–421.PubMedCrossRef
26.
go back to reference Pae HO, Jeong SO, Jeong GS, Kim KM, Kim HS, Kim SA, et al. Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells. Biochem Biophys Res Commun. 2007;353:1040–5.PubMedCrossRef Pae HO, Jeong SO, Jeong GS, Kim KM, Kim HS, Kim SA, et al. Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells. Biochem Biophys Res Commun. 2007;353:1040–5.PubMedCrossRef
27.
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
28.
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
29.
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
30.
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
31.
go back to reference Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci. 2009;30:85–94.PubMedCrossRef Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci. 2009;30:85–94.PubMedCrossRef
32.
go back to reference Tong QS, Zheng LD, Lu P, Jiang FC, Chen FM, Zeng FQ, et al. Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells. Anticancer Drugs. 2006;17:279–87.PubMedCrossRef Tong QS, Zheng LD, Lu P, Jiang FC, Chen FM, Zeng FQ, et al. Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells. Anticancer Drugs. 2006;17:279–87.PubMedCrossRef
33.
go back to reference Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res. 2001;21:873–8.PubMed Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res. 2001;21:873–8.PubMed
34.
go back to reference Rashmi R, Kumar S, Karunagaran D. Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis. Carcinogenesis. 2004;25:179–87.PubMedCrossRef Rashmi R, Kumar S, Karunagaran D. Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis. Carcinogenesis. 2004;25:179–87.PubMedCrossRef
36.
go back to reference Kajstura M, Halicka HD, Pryjma J, Darzynkiewicz Z. Discontinuous fragmentation of nuclear DNA during apoptosis revealed by discrete “sub-G1” peaks on DNA content histograms. Cytometry A. 2007;71:125–31.PubMed Kajstura M, Halicka HD, Pryjma J, Darzynkiewicz Z. Discontinuous fragmentation of nuclear DNA during apoptosis revealed by discrete “sub-G1” peaks on DNA content histograms. Cytometry A. 2007;71:125–31.PubMed
Metadata
Title
Glucose-Regulated Protein 78 (GRP78) Mediated the Efficacy to Curcumin Treatment on Hepatocellular Carcinoma
Authors
Yu-Jia Chang, PhD
Cheng-Jeng Tai, MD
Li-Jen Kuo, MD
Po-Li Wei, MD, PhD
Hung-Hua Liang, MD
Tsan-Zon Liu, PhD
Weu Wang, MD
Chen-Jei Tai, MD, PhD
Yuan-Soon Ho, PhD
Chih-Hsiung Wu, MD, PhD
Ming-Te Huang, MD
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 8/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1597-3

Other articles of this Issue 8/2011

Annals of Surgical Oncology 8/2011 Go to the issue