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Tumor Biology
Erschienen in: Tumor Biology 2/2015

01.02.2015 | Research Article

GRP78 mediates the therapeutic efficacy of curcumin on colon cancer

verfasst von: Yu-Jia Chang, Chien-Yu Huang, Chin-Sheng Hung, Wei-Yu Chen, Po-Li Wei

Erschienen in: Tumor Biology | Ausgabe 2/2015

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Abstract

Glucose-regulated protein 78 (GRP78) is the key regulator of endoplasmic reticular (ER) function. Expression of GRP78 was correlated with malignancy in different cancers. However, the role of GRP78 in the cytotoxic effect of curcumin on colon cancer cells is still unclear. A silencing RNA (siRNA) technique was used to knock down GRP78 expression. The anticancer effects of curcumin were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell cycle analysis, and a terminal dexynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. HT-29 cells expressed lower GRP78 compared with DLD-1 cells. The MTT assay revealed that HT-29 cells were more resistant to curcumin treatment than DLD-1 cells. GRP78KD cells showed more resistance to curcumin treatment compared with scrambled control cells. Overexpressed GRP78 in HT-29 cells increased the sensitivity to curcumin treatment. According to the cell cycle analysis and TUNEL assay, we found that apoptosis dramatically increased in scrambled control cells compared to GRP78KD DLD-1 cells after curcumin treatment. Finally, we evaluated levels of Bcl-2, BAX, and Bad and found that an increase of Bcl-2 level was observed in GRP78KD cells treated with curcumin. Those results were consistent with the increasing of resistance to curcumin after silencing of GRP78. The levels of GRP78 expression might determine the therapeutic efficacy of curcumin against colon cancer cells.
Literatur
1.
Basnet P, Skalko-Basnet N. Curcumin: an anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules. 2011;16:4567–98.CrossRefPubMed
2.
Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clinic Experiment Pharmacol Physiol. 2012;39:283–99.CrossRef
3.
Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, et al. Biological activities of curcumin and its analogues (congeners) made by man and mother nature. Biochem Pharmacol. 2008;76:1590–611.CrossRefPubMed
4.
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.CrossRefPubMed
5.
Shehzad A, Lee YS. Molecular mechanisms of curcumin action: signal transduction. Biofactors. 2013;39:27–36.CrossRefPubMed
6.
7.
Park W, Amin AR, Chen ZG, Shin DM. New perspectives of curcumin in cancer prevention. Cancer Prev Res (Phila). 2013;6:387–400.CrossRef
8.
Hasima N, Aggarwal BB. Cancer-linked targets modulated by curcumin. Int J Biochem Molec Biol. 2012;3:328–51.
9.
10.
11.
Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62:919–30.CrossRefPubMed
12.
Li J, Lee AS. Stress induction of grp78/bip and its role in cancer. Curr Mol Med. 2006;6:45–54.CrossRefPubMed
13.
Lee E, Nichols P, Spicer D, Groshen S, Yu MC, Lee AS. Grp78 as a novel predictor of responsiveness to chemotherapy in breast cancer. Cancer Res. 2006;66:7849–53.CrossRefPubMed
14.
Zhu X, Lin MC, Fan W, Tian L, Wang J, Ng SS, et al. An intronic polymorphism in grp78 improves chemotherapeutic prediction in non-small cell lung cancer. Chest. 2012;141:1466–72.CrossRefPubMed
15.
Pootrakul L, Datar RH, Shi SR, Cai J, Hawes D, Groshen SG, et al. Expression of stress response protein grp78 is associated with the development of castration-resistant prostate cancer. Clin Cancer Res. 2006;12:5987–93.CrossRefPubMed
16.
Delie F, Petignat P, Cohen M. Grp78 protein expression in ovarian cancer patients and perspectives for a drug-targeting approach. J Oncol. 2012;2012:468615.CrossRefPubMedPubMedCentral
17.
Wang HQ, Du ZX, Zhang HY, Gao DX. Different induction of grp78 and chop as a predictor of sensitivity to proteasome inhibitors in thyroid cancer cells. Endocrinology. 2007;148:3258–70.CrossRefPubMed
18.
Li Z, Zhang L, Zhao Y, Li H, Xiao H, Fu R, et al. Cell-surface grp78 facilitates colorectal cancer cell migration and invasion. Int J Biochem Cell Biol. 2013;45:987–94.CrossRefPubMed
19.
Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS. Endoplasmic reticulum chaperone protein grp78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem. 2003;278:20915–24.CrossRefPubMed
20.
Ranganathan AC, Zhang L, Adam AP, Aguirre-Ghiso JA. Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells. Cancer Res. 2006;66:1702–11.CrossRefPubMedPubMedCentral
21.
Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009;18:1688–94.CrossRefPubMed
22.
Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59:366–78.CrossRefPubMed
23.
Benson 3rd AB, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.CrossRefPubMed
24.
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.CrossRefPubMed
25.
El Zouhairi M, Charabaty A, Pishvaian MJ. Molecularly targeted therapy for metastatic colon cancer: proven treatments and promising new agents. Gastrointest Cancer Res. 2011;4:15–21.PubMedPubMedCentral
26.
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.CrossRefPubMed
27.
Wu CT, Wang WC, Chen MF, Su HY, Chen WY, Wu CH, et al. Glucose-regulated protein 78 mediates hormone-independent prostate cancer progression and metastasis through maspin and cox-2 expression. Tumour Biol J Int Soc Oncodeve Biol Med. 2014;35:195–204.CrossRef
28.
Tai CJ, Wang JW, Su HY, Wang CK, Wu CT, Lien YC, et al. Glucose-regulated protein 94 modulates the therapeutic efficacy to taxane in cervical cancer cells. Tumour Biol J Int Soc Oncodeve Biol Med. 2014;35:403–10.CrossRef
29.
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.CrossRefPubMed
30.
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.CrossRefPubMed
31.
Chen B, Zhang Y, Wang Y, Rao J, Jiang X, Xu Z: Curcumin inhibits proliferation of breast cancer cells through nrf2-mediated down-regulation of fen1 expression. The Journal of Steroid Biochemistry and Molecular Biology 2014.
32.
Xie YQ, Wu XB, Tang SQ. Curcumin treatment alters erk-1/2 signaling in vitro and inhibits nasopharyngeal carcinoma proliferation in mouse xenografts. Int J Clinic Experiment Med. 2014;7:108–14.
33.
Bansal SS, Goel M, Aqil F, Vadhanam MV, Gupta RC. Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila). 2011;4:1158–71.CrossRef
34.
Agrawal DK, Mishra PK. Curcumin and its analogues: potential anticancer agents. Med Res Rev. 2010;30:818–60.PubMed
35.
Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm. 2010;343:489–99.CrossRef
36.
Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinic Cancer Res Off J Am Assoc Cancer Res. 2008;14:4491–9.CrossRef
37.
Patel VB, Misra S, Patel BB, Majumdar AP. Colorectal cancer: chemopreventive role of curcumin and resveratrol. Nutr Cancer. 2010;62:958–67.CrossRefPubMed
38.
Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62:1137–41.CrossRefPubMed
39.
Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol. 2011;68:157–64.CrossRefPubMed
40.
Grynkiewicz G, Slifirski P. Curcumin and curcuminoids in quest for medicinal status. Acta Biochim Pol. 2012;59:201–12.PubMed
41.
Shehzad A, Lee J, Huh TL, Lee YS: Curcumin induces apoptosis in human colorectal carcinoma (hct-15) cells by regulating expression of prp4 and p53. Molecules and cells 2013.
42.
Kim HJ, Park SY, Park OJ, Kim YM. Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway. Molec Med Rep. 2013;8:282–6.
43.
Teiten MH, Dicato M, Diederich M: Curcumin as a regulator of epigenetic events. Molecular nutrition & food research 2013.
44.
Pichu S, Krishnamoorthy S, Shishkov A, Zhang B, McCue P, Ponnappa BC. Knockdown of ki-67 by dicer-substrate small interfering rna sensitizes bladder cancer cells to curcumin-induced tumor inhibition. PLoS One. 2012;7:e48567.CrossRefPubMedPubMedCentral
45.
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.CrossRefPubMed
46.
Sato M, Yao VJ, Arap W, Pasqualini R. Grp78 signaling hub a receptor for targeted tumor therapy. Adv Genet. 2010;69:97–114.PubMed
47.
Brostrom MA, Brostrom CO. Calcium dynamics and endoplasmic reticular function in the regulation of protein synthesis: implications for cell growth and adaptability. Cell Calcium. 2003;34:345–63.CrossRefPubMed
48.
Wang JY, Chen BK, Wang YS, Tsai YT, Chen WC, Chang WC, et al. Involvement of store-operated calcium signaling in egf-mediated cox-2 gene activation in cancer cells. Cell Signal. 2012;24:162–9.CrossRefPubMed
Metadaten
Titel
GRP78 mediates the therapeutic efficacy of curcumin on colon cancer
verfasst von
Yu-Jia Chang
Chien-Yu Huang
Chin-Sheng Hung
Wei-Yu Chen
Po-Li Wei
Publikationsdatum
01.02.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2640-3

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