J Breast Cancer.  2008 Jun;11(2):49-55. 10.4048/jbc.2008.11.2.49.

A Novel Therapeutic Approach to Breast Cancer using a Selective Cyclooxygenase 2 Inhibitor and Adenovirus-mediated Delivery of the Melanoma Differentiationassociated Gene-7 (Ad-mda7)

Affiliations
  • 1Department of Surgery, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
  • 2Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. khunt@mdanderson.org

Abstract

Recently, many preclinical and clinical researches have focused on the possible roles of new therapeutic modalities to enhance current treatment efficacy or to extend the current limitations against breast cancer treatment. Th melanoma differentiation-associated gene-7 (mda-7 ), now classified as a member of the interleukin (IL)-10 gene family, has attracted attentions from several investigators for its unique ability to act against various cancers including breast cancer. In addition to mda-7, highly selective cyclooxygenase-2 (Cox-2) inhibitors, have continuously demonstrated possible anticancer effects against various cancers even though theray with many of the inhibitors has resulted in major set backs due to complications after long-term use. However, few have performed to demonstrate the synergistic effects of these two efficient treatment options or to demonstrate preventive measures to reduce the size of tumors. We summarize important results and our experience related to the use of a selective cyclooxygenase 2 inhibitor and adenovirus-mediated delivery of mda-7.

Keyword

mda-7; Celecoxib; Breast Cancer

MeSH Terms

Attention
Breast
Breast Neoplasms
Celecoxib
Cyclooxygenase 2
Humans
Interleukins
Melanoma
Prostaglandin-Endoperoxide Synthases
Pyrazoles
Research Personnel
Sulfonamides
Treatment Outcome
Cyclooxygenase 2
Interleukins
Prostaglandin-Endoperoxide Synthases
Pyrazoles
Sulfonamides

Reference

1. The Korea Breast Cancer Society. Clinical characteristics of Korean breast cancer patients in 1998. The Korean Breast Cancer Society. J Korean Med Sci. 2000. 15:569–579.
2. Mahasreshti PJ, Kataram M, Wu H, Yalavarthy LP, Carey D, Fisher PB, et al. Ovarian cancer targeted adenoviral-mediated mda-7/IL-24 gene therapy. Gynecol Oncol. 2006. 100:521–532.
Article
3. Zhao L, Gu J, Dong A, Zhang Y, Zhong L, He L, et al. Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther. 2005. 16:845–858.
Article
4. Chen WY, Cheng YT, Lei HY, Chang CP, Wang CW, Chang MS. IL-24 inhibits the growth of hepatoma cells in vivo. Genes Immun. 2005. 6:493–499.
Article
5. Ramesh R, Ito I, Gopalan B, Saito Y, Mhashilkar AM, Chada S. Ectopic production of MDA-7/IL-24 inhibits invasion and migration of human lung cancer cells. Mol Ther. 2004. 9:510–518.
Article
6. Lebedeva IV, Su ZZ, Sarkar D, Kitada S, Dent P, Waxman S, et al. Melanoma differentiation associated gene-7, mda-7/interleukin-24, induces apoptosis in prostate cancer cells by promoting mitochondrial dysfunction and inducing reactive oxygen species. Cancer Res. 2003. 63:8138–8144.
7. Su ZZ, Lebedeva V, Sarkar D, Gopalkrishnan RV, Sauane M, Sigmon C, et al. Melanoma differentiation associated gene-7, mda7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant gliomas in a p53-independent manner. Oncogene. 2003. 22:1164–1180.
Article
8. Yacoub A, Mitchell C, Brannon J, Rosenberg E, Quao L, McKinstry R, et al. MDA-7 (interleukin-24) inhibits the proliferation of renal carcinoma cells and interacts with free radicals to promote cell death and loss of reproductive capacity. Mol Cancer Ther. 2003. 2:623–632.
9. Saeki T, Mhashilkar A, Swanson X, Zou-Yang XH, Sieger K, Kawabe S, et al. Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo. Oncogene. 2002. 21:4558–4566.
Article
10. Mhashilkar AM, Stewart AL, Sieger K, Yang HY, Khimani AH, Ito I, et al. MDA-7 negatively regulates the beta-catenin and PI3K signaling pathways in breast and lung tumor cells. Mol Ther. 2003. 8:207–219.
Article
11. Lebedeva IV, Su ZZ, Chang Y, Kitada S, Reed JC, Fisher PB. The cancer growth suppressing gene mda-7 induces apoptosis selectively in human melanoma cells. Oncogene. 2002. 21:708–718.
Article
12. Huang EY, Madireddi MT, Gopalkrishnan RV, Leszczyniecka M, Su Z, Lebedeva IV, et al. Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene. 2001. 20:7051–7063.
Article
13. Saeki T, Mhashilkar A, Chada S, Branch C, Roth JA, Ramesh R. Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro. Gene Ther. 2000. 7:2051–2057.
Article
14. Sauane M, Gopalkrishnan RV, Sarkar D, Su ZZ, Lebedeva IV, Dent P, et al. MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev. 2003. 14:35–51.
Article
15. Caudell EG, Mumm JB, Poindexter N, Ekmekcioglu S, Mhashilkar AM, Yang XH, et al. The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol. 2002. 168:6041–6046.
Article
16. Ellerhorst JA, Prieto VG, Ekmekcioglu S, Broemeling L, Yekell S, Chada S, et al. Loss of MDA-7 expression with progression of melanoma. J Clin Oncol. 2002. 20:1069–1074.
Article
17. Jiang H, Lin JJ, Su ZZ, Goldstein NI, Fisher PB. Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. Oncogene. 1995. 11:2477–2486.
18. Jiang H, Su ZZ, Lin JJ, Goldstein NI, Young CS, Fisher PB. The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. Proc Natl Acad Sci USA. 1996. 93:9160–9165.
Article
19. Su ZZ, Madireddi MT, Lin JJ, Young CS, Kitada S, Reed JC, et al. The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice. Proc Natl Acad Sci USA. 1998. 95:14400–14405.
Article
20. Madireddi MT, Dent P, Fisher PB. Regulation of mda-7 gene expression during human melanoma differentiation. Oncogene. 2000. 19:1362–1368.
Article
21. Madireddi MT, Dent P, Fisher PB. AP-1 and C/EBP transcription factors contribute to mda-7 gene promoter activity during human melanoma differentiation. J Cell Physiol. 2000. 185:36–46.
Article
22. Ekmekcioglu S, Ellerhorst J, Mhashilkar AM, Sahin AA, Read CM, Prieto VG, et al. Down-regulated melanoma differentiation associated gene (mda-7) expression in human melanomas. Int J Cancer. 2001. 94:54–59.
Article
23. Sarkar D, Su ZZ, Lebedeva IV, Sauane M, Gopalkrishnan RV, Valerie K, et al. mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK. Proc Natl Acad Sci USA. 2002. 99:10054–10059.
Article
24. Chada S, Bocangel D, Ramesh R, Grimm EA, Mumm JB, Mhashilkar AM, et al. mda-7/IL2 kills pancreatic cancer cells by inhibition of the Wnt/PI3K signaling pathways: identification of IL-20 receptormediated bystander activity against pancreatic cancer. Mol Ther. 2005. 11:724–733.
Article
25. Cao XX, Mohuiddin I, Chada S, Mhashilkar AM, Ozvaran MK, McConkey DJ, et al. Adenoviral transfer of mda-7 leads to BAX up-regulation and apoptosis in mesothelioma cells, and is abrogated by overexpression of BCL-XL. Mol Med. 2002. 8:869–876.
Article
26. Sauane M, Gopalkrishnan RV, Lebedeva I, Mei MX, Sarkar D, Su ZZ, et al. Mda-7/IL-24 induces apoptosis of diverse cancer cell lines through JAK/STAT-independent pathways. J Cell Physiol. 2003. 196:334–345.
Article
27. Ramesh R, Mhashilkar AM, Tanaka F, Saito Y, Branch CD, Sieger K, et al. Melanoma differentiation-associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor. Cancer Res. 2003. 63:5105–5113.
28. Chen J, Chada S, Mhashilkar A, Miano JM. Tumor suppressor MDA-7/IL-24 selectively inhibits vascular smooth muscle cell growth and migration. Mol Ther. 2003. 8:220–229.
Article
29. Yacoub A, Mitchell C, Lebedeva IV, Sarkar D, Su ZZ, McKinstry R, et al. mda-7 (IL-24) inhibits growth and enhances radiosensitivity of glioma cells in vitro via JNK signaling. Cancer Biol Ther. 2003. 2:347–353.
Article
30. Gopalan B, Litvak A, Sharman S, Mhashilkar AM, Chada S, Ramesh R. Activation of the Fas-FasL signaling pathway by MDA-7/IL-24 kills human ovarian cancer cells. Cancer Res. 2005. 65:3017–3024.
Article
31. van Ryn J, Pairet M. Selective cyclooxygenase-2 inhibitors: pharmacology, clinical effects and therapeutic potential. Expert Opin Investig Drugs. 1997. 6:609–614.
Article
32. Dogne JM, Hansen J, Supuran C, Pratico D. Coxibs and cardiovascular side-effects: from light to shadow. Curr Pharm Des. 2006. 12:971–975.
Article
33. Harris RE, Beebe-Donk J, Alshafie GA. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer. 2006. 6:27.
Article
34. Kundu N, Walser TC, Ma X, Fulton AM. Cyclooxygenase inhibitors modulate NK activities that control metastatic disease. Cancer Immunol Immunother. 2005. 54:981–987.
Article
35. Basu GD, Pathangey LB, Tinder TL, Lagiola M, Gendler SJ, Mukherjee P. Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in a in vivo model of spontaneous metastatic breast cancer. Mol Cancer Res. 2004. 2:632–642.
36. Guastalla JP, Bachelot T, Ray-Coquard I. Cyclooxygenase 2 and breast cancer. From biological concept to clinical trials. Bull Cancer. 2004. 91:S2. S99–S108.
37. Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ. Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer. 2001. 8:97–114.
Article
38. Hsu AL, Ching TT, Wang DS, Song X, Rangnekar VM, Chen CS. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem. 2000. 275:11397–11403.
Article
39. Yamada Y, Yoshimi N, Hirose Y, Hara A, Shimizu M, Kuno T, et al. Suppression of occurrence and advancement of beta-catenin-accumulated crypts, possible premalignant lesions of colon cancer, by selective cyclooxygenase-2 inhibitor, celecoxib. Jpn J Cancer Res. 2001. 92:617–623.
Article
40. Alshafie GA, Abou-Issa HM, Seibert K, Harris RE. Chemotherapeutic evaluation of Celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model. Oncol Rep. 2000. 7:1377–1381.
Article
41. Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 1998. 58:409–412.
42. Han C, Leng J, Demetris AJ, Wu T. Cyclooxygenase-2 promotes human cholangiocarcinoma growth: evidence for cyclooxygenase-2-independent mechanism in celecoxib-mediated induction of p21waf1/cip1 and p27kip1 and cell cycle arrest. Cancer Res. 2004. 64:1369–1376.
Article
43. Johnson AJ, Song X, Hsu A, Chen C. Apoptosis signaling pathways mediated by cyclooxygenase-2 inhibitors in prostate cancer cells. Adv Enzyme Regul. 2001. 41:221–235.
Article
44. Dvory-Sobol H, Cohen-Noyman E, Kazanov D, Figer A, Birkenfeld S, Madar-Shapiro L, et al. Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner. Eur J Cancer. 2006. 42:422–426.
Article
45. Vanchieri C. Researchers plan to continue to study COX-2 inhibitors in cancer treatment and prevention. J Natl Cancer Inst. 2005. 97:552–553.
Article
46. Arun B, Goss P. The role of COX-2 inhibition in breast cancer treatment and prevention. Semin Oncol. 2004. 31(2):Suppl 7. 22–29.
Article
47. Lanza-Jacoby S, Miller S, Flynn J, Gallatig K, Daskalakis C, Masferrer JL, et al. The cyclooxygenase-2 inhibitor, celecoxib, prevents the development of mammary tumors in Her-2/neu mice. Cancer Epidemiol Biomarkers Prev. 2003. 12:1486–1491.
48. Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ. Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem. 2002. 277:18649–18657.
49. Degner SC, Kemp MQ, Bowden GT, Romagnolo DF. Conjugated linoleic acid attenuates cyclooxygenase-2 transcriptional activity via an anti-AP-1 mechanism in MCF-7 breast cancer cells. J Nutr. 2006. 136:421–427.
Article
50. Kim SH, Hwang CI, Park WY, Lee JH, Song YS. GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells. Carcinogenesis. 2007. 28:223–231.
Article
51. Singh B, Berry JA, Shorer A, Lucci A. COX-2 induce IL-11 production in human breast cancer cells. J Surg Res. 2006. 131:267–275.
52. Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau YJ, et al. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004. 64:4309–4318.
Article
53. Kucab JE, Lee C, Chen CS, Zhu J, Gilks CB, Cheang M, et al. Celecoxib analogues disrupt Akt signaling, which is commonly activated in primary breast tumours. Breast Cancer Res. 2005. 7:R796–R807.
Article
54. Maier TJ, Janssen A, Schmidt R, Geisslinger G, Grosch S. Targeting the beta-catenin/APC pathway: a novel mechanism to explain the cyclooxygenase-2-independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. FASEB J. 2005. 19:1353–1355.
Article
55. Andrews HN, Habibi G, Kucab JE, Dunn SE. Celecoxib inhibits urokinase-type plasminogen activator (uPA) production in MDA-MB-231 breast cancer cells. Breast Cancer Res Treat. 2005. 94:47–52.
Article
56. Liu X, Yue P, Zhou Z, Khuri FR, Sun SY. Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells. J Natl Cancer Inst. 2004. 96:1769–1780.
Article
57. Ding H, Han C, Zhu J, Chen CS, D'Ambrosio SM. Celecoxib derivatives induce apoptosis via the disruption of mitochondrial membrane potential and activation of caspase 9. Int J Cancer. 2005. 113:803–810.
Article
58. Basu GD, Pathangey LB, Tinder TL, Gendler SJ, Mukherjee P. Mechanisms underlying the growth inhibitory effects of the cyclooxygenase-2 inhibitor celecoxib in human breast cancer cells. Breast Cancer Res. 2005. 7:R422–R435.
Article
59. Shishodia S, Koul D, Aggarwal BB. Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human on-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. J Immunol. 2004. 173:2011–2022.
Article
60. McKenzie T, Liu Y, Fanale M, Swisher SG, Chada S, Hunt KK. Combination therapy of Ad-mda7 and trastuzumab increases cell death in Her-2/neu-overexpressing breast cancer cells. Surgery. 2004. 136:437–442.
Article
61. Fulzele SV, Shaik MS, Chatterjee A, Singh M. Anti-cancer effect of celecoxib and aerosolized docetaxel against human non-small cell lung cancer cell line, A549. J Pharm Pharmacol. 2006. 58:327–336.
Article
62. Ferrari V, Valcamonico F, Amoroso V, Simoncini E, Vassalli L, Marpicati P, et al. Gemcitabine plus celecoxib (GECO) in advanced pancreatic cancer: a phase II trial. Cancer Chemother Pharmacol. 2006. 57:185–190.
Article
63. Csiki I, Morrow JD, Sandler A, Shyr Y, Oates J, Williams MK, et al. Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phae II trial of celecoxib and docetaxel. Clin Cancer Res. 2005. 11:6634–6640.
Article
64. Dandekar DS, Lopez M, Carey RI, Lokeshwar BL. Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-2 and -9 in prostate cancer cells. Int J Cancer. 2005. 115:484–492.
Article
65. Chow LW, Cheng CW, Wong JL, Toi M. Serum lipid profiles in patients receiving endocrine treatment for breast cancer the results from the Celecoxib Anti-Aromatase Neoadjuvant (CAAN) Trial. Biomed Pharmacother. 2005. 59:S2. S302–S305.
66. Chow LW, Loo WT, Wai CC, Lui EL, Zhu L, Toi M. Study of COX-2, Ki67, and p53 expression to predict effectiveness of 5-fluorouracil, epirubicin and cyclophosphamide with celecoxib treatment in breast cancer patients. Biomed Pharmacother. 2005. 59:S2. S298–S301.
67. Bundred NJ, Bames NL. Potential use of COX-2-aromatase inhibitor combinations in breast cancer. Br J Cancer. 2005. 93:S1. S10–S15.
Article
68. Suh YJ, Chada S, McKenzie T, Liu Y, Swisher SG, Lucci A, et al. Synergistic tumoricidal effect between celecoxib and adenoviral-mediated delivery of mda-7 in human breast cancer cells. Surgery. 2005. 138:422–430.
Article
69. Oida Y, Gopalan B, Miyahara R, Inoue S, Branch CD, Mhashilkar AM, et al. Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005. 4:291–304.
70. Guo S, Sonenshein GE. Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is replaced by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol. 2004. 24:8681–8690.
Article
71. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002. 347:1227–1232.
Article
72. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002. 347:1233–1241.
Article
73. Chada S, Mhashilkar AM, Liu Y, Nishikawa T, Bocangel D, Zheng M, et al. mda-7 gene transfer sensitizes breast carcinoma cells to chemotherapy, biologic therapies and radiotherapy: correlation with expression of bcl-2 family members. Cancer Gene Ther. 2006. 13:490–502.
Article
74. Kawabe S, Nishikawa T, Munshi A, Roth JA, Chada S, Meyn RE. Adenovirus-mediated mda-7 gene expression radiosensitizes non-small cell lung cancer cells via TP53-independent mechanisms. Mol Ther. 2002. 6:637–644.
Article
75. Awara WM, El-Sisi AE, El-Sayad ME, Goda AE. The potential role of cyclooxygenase-2 inhibitors in the treatment of experimentally-induced mammary tumour: does celecoxib enhance the anti-tumour activity of doxorubicin? Pharmacol Res. 2004. 50:487–498.
Article
76. Merchan JR, Jayaram DR, Supko JG, He X, Bubley GJ, Sukhatme VP. Increased endothelial uptake of paclitaxel as a potential mechanism for its Antiangiogenic effects: potentiation by Cox-2 inhibition. Int J Cancer. 2005. 113:490–498.
Article
77. Shin YK, Park JS, Kim HS, Jun HJ, Kim GE, Suh CO, et al. Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer Res. 2005. 65:9501–9509.
Article
78. Raju U, Ariga H, Dittmann K, Nakata E, Ang KK, Milas L. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. Int J Radiat Oncol Biol Phys. 2005. 63:520–528.
Article
79. Cerchietti LC, Bonomi MR, Navigante AH, Castro MA, Cabalar ME, Roth BM. Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases. J Neurooncol. 2005. 71:73–81.
Article
80. Su ZZ, Lebedeva IV, Sarkar D, Emdad L, Gupta P, Kitada S, et al. Ionizing radiation enhances therapeutic activity of mda-7/IL-24: overcoming radiation- and mda-7/IL-24-resistance in prostate cancer cells overexpressing the antiapoptotic proteins bcl-x(L) or bcl-2. Oncogene. 2006. 25:2339–2348.
Article
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