Sequential treatment with celecoxib and bortezomib enhances the ER stress‑mediated autophagy‑associated cell death of colon cancer cells

Park,Ga‑Bin; Jin,Dong‑Hoon; Kim,Daejin

doi:10.3892/ol.2018.9233

Sequential treatment with celecoxib and bortezomib enhances the ER stress‑mediated autophagy‑associated cell death of colon cancer cells

Authors:
- Ga‑Bin Park
- Dong‑Hoon Jin
- Daejin Kim
View Affiliations

Affiliations: Department of Biochemistry, Kosin University College of Medicine, Busan 49267, Republic of Korea, Department of Convergence, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea, Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea
Published online on: July 30, 2018 https://doi.org/10.3892/ol.2018.9233
Pages: 4526-4536
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Treatment with celecoxib and bortezomib as single chemotherapeutic agents reduces the viability and proliferation of colorectal cancer cells. The use of these agents in combination with other chemotherapeutic agents is usually associated with adverse effects. In the present study, a combination of celecoxib and bortezomib was investigated for potential synergistic effects in colon cancer cells. The sequential exposure to celecoxib with bortezomib synergistically induced apoptotic death in human colon cancer cells compared with groups treated with a single drug or other drug combinations. c‑Jun N‑terminal kinase/p38‑mitogen‑activated protein kinase‑induced endoplasmic reticulum (ER) stress through serial exposure to celecoxib and bortezomib may have induced the intracellular Ca2+ release, leading to the generation of autophagosomes in p53‑expressing HCT‑116 cells. Targeted inhibition of p53 activity or ER stress or treatment with the Ca2+‑chelating agent BAPTA‑AM suppressed the ER stress‑mediated Ca2+ release and apoptosis. Although p53‑/‑ HCT‑116 cells were less sensitive to sequential treatment with celecoxib and bortezomib, co‑localization of autophagosomes was detected in the absence of CCAAT‑enhancer‑binding protein homologous protein expression. Treatment of p53‑/‑ HCT‑116 cells with BAPTA‑AM did not inhibit apoptosis following serial treatment with celecoxib and bortezomib. These results suggest that the order of drug administration is important in treating cancer and that the sequential treatment with celecoxib and bortezomib enhances the ER stress‑mediated autophagy‑associated cell death of colon cancer cells, regardless of p53 expression.

View Figures

View References

1	Arico S, Pattingre S, Bauvy C, Gane P, Barbat A, Codogno P and Ogier-Denis E: Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem. 277:27613–27621. 2002. View Article : Google Scholar : PubMed/NCBI
2	Lynch PM, Ayers GD, Hawk E, Richmond E, Eagle C, Woloj M, Church J, Hasson H, Patterson S, Half E and Burke CA: The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol. 105:1437–1443. 2010. View Article : Google Scholar : PubMed/NCBI
3	Tsutsumi S, Namba T, Tanaka KI, Arai Y, Ishihara T, Aburaya M, Mima S, Hoshino T and Mizushima T: Celecoxib upregulates endoplasmic reticulum chaperones that inhibit celecoxib-induced apoptosis in human gastric cells. Oncogene. 25:1018–1029. 2006. View Article : Google Scholar : PubMed/NCBI
4	Tsutsumi S, Gotoh T, Tomisato W, Mima S, Hoshino T, Hwang HJ, Takenaka H, Tsuchiya T, Mori M and Mizushima T: Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death Differ. 11:1009–1016. 2004. View Article : Google Scholar : PubMed/NCBI
5	Lin WC, Chuang YC, Chang YS, Lai MD, Teng YN, Su IJ, Wang CC, Lee KH and Hung JH: Endoplasmic reticulum stress stimulates p53 expression through NF-κB activation. PLoS One. 7:e391202012. View Article : Google Scholar : PubMed/NCBI
6	Edagawa M, Kawauchi J, Hirata M, Goshima H, Inoue M, Okamoto T, Murakami A, Maehara Y and Kitajima S: Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib. J Biol Chem. 289:21544–21561. 2014. View Article : Google Scholar : PubMed/NCBI
7	Ludwig H, Khayat D, Giaccone G and Facon T: Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies. Cancer. 104:1794–1807. 2005. View Article : Google Scholar : PubMed/NCBI
8	Nawrocki ST, Carew JS, Pino MS, Highshaw RA, Dunner K Jr, Huang P, Abbruzzese JL and McConkey DJ: Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res. 65:11658–11666. 2005. View Article : Google Scholar : PubMed/NCBI
9	Yu J, Tiwari S, Steiner P and Zhang L: Differential apoptotic response to the proteasome inhibitor Bortezomib [VELCADE, PS-341] in Bax-deficient and p21-deficient colon cancer cells. Cancer Biol Ther. 2:694–699. 2003. View Article : Google Scholar : PubMed/NCBI
10	Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T and Thompson CB: Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 120:237–248. 2005. View Article : Google Scholar : PubMed/NCBI
11	Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar : PubMed/NCBI
12	Yang Z and Klionsky DJ: Eaten alive: A history of macroautophagy. Nat Cell Biol. 12:814–822. 2010. View Article : Google Scholar : PubMed/NCBI
13	Kao C, Chao A, Tsai CL, Chuang WC, Huang WP, Chen GC, Lin CY, Wang TH, Wang HS and Lai CH: Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation. Cell Death Dis. 5:e15102014. View Article : Google Scholar : PubMed/NCBI
14	Huang S and Sinicrope FA: Celecoxib-induced apoptosis is enhanced by ABT-737 and by inhibition of autophagy in human colorectal cancer cells. Autophagy. 6:256–269. 2010. View Article : Google Scholar : PubMed/NCBI
15	Deniaud A, el dein Sharaf O, Maillier E, Poncet D, Kroemer G, Lemaire C and Brenner C: Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene. 27:285–299. 2008. View Article : Google Scholar : PubMed/NCBI
16	Li J, Lee B and Lee AS: Endoplasmic reticulum stress-induced apoptosis: Multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem. 281:7260–7270. 2006. View Article : Google Scholar : PubMed/NCBI
17	Giorgi C, Bonora M, Sorrentino G, Missiroli S, Poletti F, Suski JM, Ramirez Galindo F, Rizzuto R, Di Virgilio F, Zito E, et al: p53 at the endoplasmic reticulum regulates apoptosis in a Ca2+-dependent manner. Proc Natl Acad Sci USA. 112:1779–1784. 2015. View Article : Google Scholar : PubMed/NCBI
18	Kardosh A, Golden EB, Pyrko P, Uddin J, Hofman FM, Chen TC, Louie SG, Petasis NA and Schönthal AH: Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib. Cancer Res. 68:843–851. 2008. View Article : Google Scholar : PubMed/NCBI
19	Kim JE, Lee JI, Jin DH, Lee WJ, Park GB, Kim S, Kim YS, Wu TC, Hur DY and Kim D: Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2. Oncol Rep. 31:2429–2437. 2014. View Article : Google Scholar : PubMed/NCBI
20	Altorki NK, Keresztes RS, Port JL, Libby DM, Korst RJ, Flieder DB, Ferrara CA, Yankelevitz DF, Subbaramaiah K, Pasmantier MW and Dannenberg AJ: Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer. J Clin Oncol. 21:2645–2650. 2003. View Article : Google Scholar : PubMed/NCBI
21	Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ and Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 60:1306–1311. 2000.PubMed/NCBI
22	Sacchetti A: Cancer cell killing by Celecoxib: Reality or just in vitro precipitation-related artifact? J Cell Biochem. 114:1434–1444. 2013. View Article : Google Scholar : PubMed/NCBI
23	Cho HY, Thomas S, Golden EB, Gaffney KJ, Hofman FM, Chen TC, Louie SG, Petasis NA and Schönthal AH: Enhanced killing of chemo-resistant breast cancer cells via controlled aggravation of ER stress. Cancer Lett. 282:87–97. 2009. View Article : Google Scholar : PubMed/NCBI
24	Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E and Bertagnolli M: Adenoma Prevention with Celecoxib (APC) Study Investigators: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 352:1071–1080. 2005. View Article : Google Scholar : PubMed/NCBI
25	Milani M, Rzymski T, Mellor HR, Pike L, Bottini A, Generali D and Harris AL: The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib. Cancer Res. 69:4415–4423. 2009. View Article : Google Scholar : PubMed/NCBI
26	Boyce M and Yuan J: Cellular response to endoplasmic reticulum stress: A matter of life or death. Cell Death Differ. 13:363–373. 2006. View Article : Google Scholar : PubMed/NCBI
27	Cuervo AM: Autophagy: In sickness and in health. Trends Cell Biol. 14:70–77. 2004. View Article : Google Scholar : PubMed/NCBI
28	Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T and Korsmeyer SJ: Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA. 102:105–110. 2005. View Article : Google Scholar : PubMed/NCBI
29	Pinton P, Giorgi C and Pandolfi PP: The role of PML in the control of apoptotic cell fate: A new key player at ER-mitochondria sites. Cell Death Differ. 18:1450–1456. 2011. View Article : Google Scholar : PubMed/NCBI
30	Levine B, Sinha S and Kroemer G: Bcl-2 family members: Dual regulators of apoptosis and autophagy. Autophagy. 4:600–606. 2008. View Article : Google Scholar