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Cancer Cell International
Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

Curcumin induces apoptosis in gallbladder carcinoma cell line GBC-SD cells

Authors: Tian-Yu Liu, Zhu-Jun Tan, Lin Jiang, Jian-Feng Gu, Xiang-Song Wu, Yang Cao, Mao-Lan Li, Ke-Jin Wu, Ying-Bin Liu

Published in: Cancer Cell International | Issue 1/2013

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Abstract

Background

Gallbladder carcinoma is a malignant tumor with a very low 5-year survival rate because of the difficulty with its early diagnosis and the very poor prognosis of the advanced cancer state. The aims of this study were to determine whether curcumin could induce the apoptosis of a gallbladder carcinoma cell line, GBC-SD, and to clarify its related mechanism.

Methods

First, the anti-proliferative activities of curcumin-treated and untreated GBC-SD cells were determined using the MTT and colony formation assays. Then, the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay and Hoechst 33342 staining assay. Detection of mitochondrial membrane potential was used to validate the ability of curcumin on inducing apoptosis in GBC-SD cells. Cell cycle changes were detected by flow cytometric analysis. Finally, the expressions of the apoptosis-related proteins or genes caspase-3, PARP, Bcl-2, and Bax were analyzed by western blot and quantitative real time PCR assay. Statistical analyses were performed using the Student’s t-test for comparison of the results obtained from cells with or without curcumin treatment.

Results

The MTT assay revealed that curcumin had induced a dose- and a time-dependent decrease in cell viability. Colony counting indicated that curcumin had induced a dose-dependent decrease in the colony formation ability in GBC-SD cells. Cells treated with curcumin were arrested at the S phase, according to the flow cytometric analysis. A significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. Morphological changes in apoptotic cells were also found by the Hoechst 33342 staining. After treatment with curcumin fluorescence shifted from red to green as ΔΨm decreased. Furthermore, western blot and quantitative real time PCR assays demonstrated that the curcumin induced apoptosis in GBC-SD cells by regulating the ratio of Bcl-2/Bax and activating the expression of cleaved caspase-3.

Conclusions

Taken together, the results indicate that curcumin may be a potential agent for the treatment of gallbladder cancer.
Appendix
Available only for authorised users
Literature
1.
Kaza RK, Gulati M, Wig JD, Chawla YK: Evaluation of gall bladder carcinoma with dynamic magnetic resonance imaging and magnetic resonance cholangiopancreatography. Australas Radiol. 2006, 50 (3): 212-217. 10.1111/j.1440-1673.2006.01564.x.CrossRefPubMed
2.
Tan Z, Li M, Wu W, Zhang L, Ding Q, Wu X, Mu J, Liu Y: NLK is a key regulator of proliferation and migration in gallbladder carcinoma cells. Mol Cell Biochem. 2012, 369 (1–2): 27-33.CrossRefPubMed
3.
Wang JW, Peng SY, Li JT, Wang Y, Zhang ZP, Cheng Y, Cheng DQ, Weng WH, Wu XS, Fei XZ: Identification of metastasis-associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1. Cancer Lett. 2009, 281 (1): 71-81. 10.1016/j.canlet.2009.02.020.CrossRefPubMed
4.
Wang JD, Shi WB, Shen J, Zhuang PY, Quan ZW, Wang XF, Zhou XP, Li SG, Liu YB, Yang Y: Evaluation of two modified ECF regimens in the treatment of advanced gallbladder cancer. Med Oncol. 2011, 28 (Suppl 1): S295-300.CrossRefPubMed
5.
Dong P, He XW, Gu J, Wu WG, Li ML, Yang JH, Zhang L, Ding QC, Lu JH, Mu JS: Vimentin significantly promoted gallbladder carcinoma metastasis. Chin Med J (Engl). 2011, 124 (24): 4236-4244.
6.
Miller G, Jarnagin WR: Gallbladder carcinoma. Eur J Surg Oncol. 2008, 34 (3): 306-312. 10.1016/j.ejso.2007.07.206.CrossRefPubMed
7.
Shimada K, Nara S, Esaki M, Sakamoto Y, Kosuge T, Hiraoka N: Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum. Br J Surg. 2011, 98 (1): 117-123. 10.1002/bjs.7262.CrossRefPubMed
8.
Malka D, Boige V, Dromain C, Debaere T, Pocard M, Ducreux M: Biliary tract neoplasms: update 2003. Curr Opin Oncol. 2004, 16 (4): 364-371. 10.1097/01.cco.0000129679.49651.50.CrossRefPubMed
9.
Ye F, Zhang GH, Guan BX, Xu XC: Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin. World J Gastroenterol. 2012, 18 (2): 126-135. 10.3748/wjg.v18.i2.126.PubMedCentralCrossRefPubMed
10.
Saha A, Kuzuhara T, Echigo N, Fujii A, Suganuma M, Fujiki H: Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of "growth arrest and DNA damage inducible genes 45 and 153". Biol Pharm Bull. 2010, 33 (8): 1291-1299. 10.1248/bpb.33.1291.CrossRefPubMed
11.
Kumaravel M, Sankar P, Latha P, Benson CS, Rukkumani R: Antiproliferative effects of an analog of curcumin in Hep-2 cells: a comparative study with curcumin. Nat Prod Commun. 2013, 8 (2): 183-186.PubMed
12.
Guimaraes MR, Coimbra LS, de Aquino SG, Spolidorio LC, Kirkwood KL, Rossa C: Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. J Periodontal Res. 2011, 46 (2): 269-279. 10.1111/j.1600-0765.2010.01342.x.PubMedCentralCrossRefPubMed
13.
Debnath S, Saloum D, Dolai S, Sun C, Averick S, Raja K, Fata JE: Dendrimer-curcumin. 2013, A Water Soluble and Effective Cytotoxic Agent against Breast Cancer Cell Lines. Anticancer Agents Med Chem: Conjugate
14.
Faiao-Flores F, Suarez JA, Maria-Engler SS, Soto-Cerrato V, Perez-Tomas R, Maria DA: The curcumin analog DM-1 induces apoptotic cell death in melanoma. Tumour Biol. 2013, 34 (2): 1119-1129. 10.1007/s13277-013-0653-y.CrossRefPubMed
15.
Wang WZ, Li L, Liu MY, Jin XB, Mao JW, Pu QH, Meng MJ, Chen XG, Zhu JY: Curcumin induces FasL-related apoptosis through p38 activation in human hepatocellular carcinoma Huh7 cells. Life Sci. 2013, 92 (6–7): 352-358.PubMed
16.
Zhang CY, Zhang L, Yu HX, Bao JD, Lu RR: Curcumin inhibits the metastasis of K1 papillary thyroid cancer cells via modulating E-cadherin and matrix metalloproteinase-9 expression. Biotechnol Lett. 2013, 35 (7): 995-1000. 10.1007/s10529-013-1173-y.CrossRefPubMed
17.
Cheng TS, Chen WC, Lin YY, Tsai CH, Liao CI, Shyu HY, Ko CJ, Tzeng SF, Huang CY, Yang PC: Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prev Res (Phila). 2013, 6 (5): 495-505. 10.1158/1940-6207.CAPR-12-0293-T.CrossRef
18.
Liu L, Sun L, Wu Q, Guo W, Li L, Chen Y, Li Y, Gong C, Qian Z, Wei Y: Curcumin loaded polymeric micelles inhibit breast tumor growth and spontaneous pulmonary metastasis. Int J Pharm. 2013, 443 (1–2): 175-182.CrossRefPubMed
19.
Masuelli L, Benvenuto M, Fantini M, Marzocchella L, Sacchetti P, Di Stefano E, Tresoldi I, Izzi V, Bernardini R, Palumbo C: Curcumin induces apoptosis in breast cancer cell lines and delays the growth of mammary tumors in neu transgenic mice. J Biol Regul Homeost Agents. 2013, 27 (1): 105-119.PubMed
20.
Choudhury D, Ganguli A, Dastidar DG, Acharya BR, Das A, Chakrabarti G: Apigenin shows synergistic anticancer activity with curcumin by binding at different sites of tubulin. Biochimie. 2013, 95 (6): 1297-1309. 10.1016/j.biochi.2013.02.010.CrossRefPubMed
21.
Subramaniam D, Ponnurangam S, Ramamoorthy P, Standing D, Battafarano RJ, Anant S, Sharma P: Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One. 2012, 7 (2): e30590-10.1371/journal.pone.0030590.PubMedCentralCrossRefPubMed
22.
Han X, Xu B, Beevers CS, Odaka Y, Chen L, Liu L, Luo Y, Zhou H, Chen W, Shen T: Curcumin inhibits protein phosphatases 2A and 5, leading to activation of mitogen-activated protein kinases and death in tumor cells. Carcinogenesis. 2012, 33 (4): 868-875. 10.1093/carcin/bgs029.PubMedCentralCrossRefPubMed
23.
Tu SP, Jin H, Shi JD, Zhu LM, Suo Y, Lu G, Liu A, Wang TC, Yang CS: Curcumin induces the differentiation of myeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth. Cancer Prev Res (Phila). 2012, 5 (2): 205-215. 10.1158/1940-6207.CAPR-11-0247.CrossRef
24.
Quitschke WW: Curcuminoid binding to embryonal carcinoma cells: reductive metabolism, induction of apoptosis, senescence, and inhibition of cell proliferation. PLoS One. 2012, 7 (6): e39568-10.1371/journal.pone.0039568.PubMedCentralCrossRefPubMed
25.
Sahu RP, Batra S, Srivastava SK: Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. Br J Cancer. 2009, 100 (9): 1425-1433. 10.1038/sj.bjc.6605039.PubMedCentralCrossRefPubMed
26.
Miller M, Chen S, Woodliff J, Kansra S: Curcumin (diferuloylmethane) inhibits cell proliferation, induces apoptosis, and decreases hormone levels and secretion in pituitary tumor cells. Endocrinology. 2008, 149 (8): 4158-4167. 10.1210/en.2007-1760.PubMedCentralCrossRefPubMed
27.
Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP: Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res. 2008, 68 (18): 7283-7292. 10.1158/0008-5472.CAN-07-6246.PubMedCentralCrossRefPubMed
28.
Bao B, Ali S, Banerjee S, Wang Z, Logna F, Azmi AS, Kong D, Ahmad A, Li Y, Padhye S: Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res. 2012, 72 (1): 335-345. 10.1158/0008-5472.CAN-11-2182.PubMedCentralCrossRefPubMed
29.
Kelly PN, Strasser A: The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 2011, 18 (9): 1414-1424. 10.1038/cdd.2011.17.PubMedCentralCrossRefPubMed
30.
Strasser A, Cory S, Adams JM: Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J. 2011, 30 (18): 3667-3683. 10.1038/emboj.2011.307.PubMedCentralCrossRefPubMed
31.
Kroemer G, Galluzzi L, Brenner C: Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007, 87 (1): 99-163. 10.1152/physrev.00013.2006.CrossRefPubMed
32.
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S: Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 2012, 19 (1): 107-120. 10.1038/cdd.2011.96.PubMedCentralCrossRefPubMed
33.
Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN: Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993, 4 (6): 327-332.PubMed
34.
Lindsay J, Esposti MD, Gilmore AP: Bcl-2 proteins and mitochondria–specificity in membrane targeting for death. Biochim Biophys Acta. 2011, 1813 (4): 532-539. 10.1016/j.bbamcr.2010.10.017.CrossRefPubMed
35.
Walensky LD: BCL-2 in the crosshairs: tipping the balance of life and death. Cell Death Differ. 2006, 13 (8): 1339-1350. 10.1038/sj.cdd.4401992.CrossRefPubMed
36.
Plumb JA: Cell sensitivity assays: the MTT assay. Methods Mol Med. 2004, 88: 165-169.PubMed
37.
Dong P, Zhang Y, Gu J, Wu W, Li M, Yang J, Zhang L, Lu J, Mu J, Chen L: Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis, inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by inducing the expression of maspin. J Ethnopharmacol. 2011, 137 (3): 1373-1380. 10.1016/j.jep.2011.08.005.CrossRefPubMed
38.
Quan Z, Gu J, Dong P, Lu J, Wu X, Wu W, Fei X, Li S, Wang Y, Wang J: Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to cirsimaritin-induced apoptosis in human gallbladder carcinoma GBC-SD cells. Cancer Lett. 2010, 295 (2): 252-259. 10.1016/j.canlet.2010.03.008.CrossRefPubMed
Metadata
Title
Curcumin induces apoptosis in gallbladder carcinoma cell line GBC-SD cells
Authors
Tian-Yu Liu
Zhu-Jun Tan
Lin Jiang
Jian-Feng Gu
Xiang-Song Wu
Yang Cao
Mao-Lan Li
Ke-Jin Wu
Ying-Bin Liu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-64

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