The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway

Molecular Cancer

Volumn 13, Issue 1, 2014, Pages

  Ghattass, Khaled ^a   El Sitt, Sally ^a   Zibara, Kazem ^b   Rayes, Saide ^a   Haddadin, Makhluf J ^a   El Sabban, Marwan ^a   Gali Muhtasib, Hala ^a  

^a AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

^b LEBANESE UNIVERSITY   (Lebanon)

Author keywords

Breast cancer; DCQ; HIF 1 ; Hypoxia; Metastasis

Indexed keywords

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL HYPOXIA; CELL LINE, TUMOR; CELL SURVIVAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MICE; MICE, INBRED NOD; MICE, SCID; NEOPLASM INVASIVENESS; QUINOXALINES; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TRANSFECTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84892685039     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-13-12     Document Type: Article

References (46)

1. Lunt SJ, Chaudary N, Hill RP. The tumor microenvironment and metastatic disease. Clin Exp Metastasis 2009, 26:19-34. 10.1007/s10585-008-9182-2, 18543068.
2. Kallinowski F, Tyler G, Mueller-Klieser W, Vaupel P. Growth-related changes of oxygen consumption rates of tumor cells grown in vitro and in vivo. J Cell Physiol 1989, 138:183-191. 10.1002/jcp.1041380124, 2910882.
3. Sullivan R, Graham CH. Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev 2007, 26:319-331. 10.1007/s10555-007-9062-2, 17458507.
4. Hill RP, Marie-Egyptienne DT, Hedley DW. Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol 2009, 19:106-111. 10.1016/j.semradonc.2008.12.002, 19249648.
5. Koch U, Krause M, Baumann M. Cancer stem cells at the crossroads of current cancer therapy failures-radiation oncology perspective. Semin Cancer Biol 2010, 20:116-124. 10.1016/j.semcancer.2010.02.003, 20219680.
6. Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer 2006, 6:449-458. 10.1038/nrc1886, 16723991.
7. Wind NS, Holen I. Multidrug resistance in breast cancer: from in vitro models to clinical studies. Int J Breast Cancer 2011, 2011:1-12.
8. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003, 3:721-732. 10.1038/nrc1187, 13130303.
9. Koh MY, Darnay BG, Powis G. Hypoxia-associated factor, a novel E3-ubiquitin ligase, binds and ubiquitinates hypoxia-inducible factor 1alpha, leading to its oxygen-independent degradation. Mol Cell Biol 2008, 28:7081-7095. 10.1128/MCB.00773-08, 2593390, 18838541.
10. Semenza GL. HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol 2001, 13:167-171. 10.1016/S0955-0674(00)00194-0, 11248550.
11. Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer 2011, 11:393-410. 10.1038/nrc3064, 21606941.
12. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 2008, 10:295-305. 10.1038/ncb1691, 18297062.
13. Chen J, Imanaka N, Chen J, Griffin JD. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer 2010, 102:351-360. 10.1038/sj.bjc.6605486, 2816657, 20010940.
14. Lin Q, Lee YJ, Yun Z. Differentiation arrest by hypoxia. J Biol Chem 2006, 281:30678-30683. 10.1074/jbc.C600120200, 16926163.
15. Ban HS, Uto Y, Nakamura H. Hypoxia-inducible factor inhibitors: a survey of recent patented compounds (2004-2010). Expert Opin Ther Pat 2011, 21:131-146. 10.1517/13543776.2011.547477, 21210751.
16. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004, 4:437-447. 10.1038/nrc1367, 15170446.
17. McKeown SR, Cowen RL, Williams KJ. Bioreductive drugs: from concept to clinic. Clin Oncol 2007, 19:427-442.
18. Diab-Assef M, Haddadin MJ, Yared P, Assaad C, Gali-Muhtasib H. Quinoxaline 1,4-dioxides: hypoxia-selective therapeutic agents. Mol Carcinog 2002, 33:198-205. 10.1002/mc.10036, 11933073.
19. El-Khatib M, Geara F, Haddadin MJ, Gali-Muhtasib H. Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21. Radiat Oncol 2010, 5:107. 10.1186/1748-717X-5-107, 2993715, 21078189.
20. Gali-Muhtasib H, Haddadin MJ, Rahhal D, Younes IH. Quinoxaline 1,4-dioxides as anticancer and hypoxia-selective drugs. Oncol Rep 2001, 8:679-684.
21. Harakeh S, Diab-Assef M, El-Sabban M, Haddadin MJ, Gali-Muhtasib H. Inhibition of proliferation and induction of apoptosis by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide in adult T-cell leukemia cells. Chem Biol Interact 2004, 148:101-113. 10.1016/j.cbi.2004.05.002, 15276867.
22. Itani W, Geara F, Haykal J, Haddadin MJ, Gali-Muhtasib H. Radiosensitization by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide under oxia and hypoxia in human colon cancer cells. Radiat Oncol 2007, 2:1. 10.1186/1748-717X-2-1, 1770925, 17201910.
23. Gali-Muhtasib H, Sidani M, Geara F, Mona AD, Al-Hmaira J, Haddadin MJ, Zaatari G. Quinoxaline 1,4-dioxides are novel angiogenesis inhibitors that potentiate antitumor effects of ionizing radiation. Int J Oncol 2004, 24:1121-1131.
24. Haykal J, Geara F, Haddadin MJ, Gali-Muhtasib H. The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide induces DNA damage in EMT-6 mammary carcinoma cells. Radiat Oncol 2009, 4:25. 10.1186/1748-717X-4-25, 2716350, 19594955.
25. Chaudary N, Hill RP. Hypoxia and metastasis in breast cancer. Breast Dis 2007, 26:55-64.
26. Favaro E, Lord S, Harris AL, Buffa FM. Gene expression and hypoxia in breast cancer. Genome Med 2011, 3:55. 10.1186/gm271, 3238181, 21875443.
27. Nagaraja GM, Othman M, Fox BP, Alsaber R, Pellegrino CM, Zeng Y, Khanna R, Tamburni P, Swaroop A, Kandpal RP. Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics. Oncogene 2006, 16:2328-2338.
28. Kaluzová M, Kaluz S, Lerman MI, Stanbridge EJ. DNA damage is a prerequisite for p53-mediated proteasomal degradation of HIF-1alpha in hypoxic cells and downregulation of the hypoxia marker carbonic anhydrase IX. Mol Cell Biol 2004, 24:5757-5766. 10.1128/MCB.24.13.5757-5766.2004, 480909, 15199132.
29. Zhang J, Cao J, Weng Q, Wu R, Yan Y, Jing H, Zhu H, He Q, Yang B. Suppression of hypoxia-inducible factor 1α (HIF-1α) by tirapazamine is dependent on eIF2α phosphorylation rather than the mTORC1/4E-BP1 pathway. PLoS One 2010, 5:13910.
30. Milani M, Harris AL. Targeting tumour hypoxia in breast cancer. Eur J Cancer 2008, 44:2766-2773. 10.1016/j.ejca.2008.09.025, 18990559.
31. Lalani AS, Alters SE, Wong A, Albertella MR, Cleland JL, Henner WD. Selective tumor targeting by the hypoxia-activated prodrug AQ4N blocks tumor growth and metastasis in preclinical models of pancreatic cancer. Clin Cancer Res 2007, 13:2216-2225. 10.1158/1078-0432.CCR-06-2427, 17404106.
32. Miyake K, Nishioka M, Imura S, Batmunkh E, Uto Y, Nagasawa H, Hori H, Shimada M. The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1α targeted gene expression. Exp Cell Res 2012, 318:1554-1563. 10.1016/j.yexcr.2012.03.013, 22472348.
33. Miyake K, Shimada M, Nishioka M, Sugimoto K, Batmunkh E, Uto Y, Nagasawa H, Hori H. The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer. Cancer Lett 2008, 272:325-335. 10.1016/j.canlet.2008.07.020, 18762366.
34. Rischin D, Peters L, Fisher R, Macann A, Denham J, Poulsen M, Jackson M, Kenny L, Penniment M, Corry J, Lamb D, McClure B. Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02). J Clin Oncol 2005, 23:79-87. 10.1200/JCO.2005.01.072, 15625362.
35. Rischin D, Peters LJ, O'Sullivan B, Giralt J, Fisher R, Yuen K, Trotti A, Bernier J, Bourhis J, Ringash J, Henke M, Kenny L. Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, Head START): a phase III trial of the Trans-Tasman Radiation Oncology Group. J Clin Oncol 2010, 28:2989-2995. 10.1200/JCO.2009.27.4449, 20479425.
36. Sayed Alwi S, Cavell BE, Donely A, Packman G. Differential induction of apoptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent. Cell Stress Chaperones 2012, 5:529-538.
37. Currie MJ, Beardsley BE, Harris GC, Gunningham SP, Dachs GU, Dijkstra B, Morrin HR, Wells JE, Robinson BA. Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: relationships with markers of tumor hypoxia and microvascularity. Hum Pathol 2012, 12:8177-8182.
38. Li J, Zucker S, Pulkoski-Gross A, Kuscu C, Karaayvaz M, Ju J, Yao H, Song E, Cao J. Conversion of stationary to invasive tumor initiating cells (TICs): role of hypoxia in membrane type 1-matrix metalloproteinase (MT1-MMP) trafficking. PLoS 2012, 7:38403.
39. Schwab LP, Peacock DL, Majumdar D, Ingels JF, Jensen LC, Smith KD, Cushing RC, Seagroves TN. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res 2012, 14:R6. 10.1186/bcr3087, 3496121, 22225988.
40. Wong CCL, Zhang H, Gilkes DM, Chen J, Wei H, Chaturvedi P, Hubbi ME, Semenza GL. Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis. J Mol Med 2012, 90:803-815. 10.1007/s00109-011-0855-y, 3437551, 22231744.
41. Ghattass K, Assah R, El-Sabban M, Gali-Muhtasib H. Targeting hypoxia for sensitization of tumors to radio- and chemotherapy. Curr Cancer Drug Targets 2013, 13:670-685. 10.2174/15680096113139990004, 23687923.
42. Del Bufalo D, Ciuffreda L, Trisciuoglio D, Desideri M, Cognetti F, Zupi G, Milella M. Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus. Cancer Res 2006, 66:5549-5554. 10.1158/0008-5472.CAN-05-2825, 16740688.
43. Balamurugan K, Wang JM, Tsai HH, Sharan S, Anver M, Leighty R, Sterneck E. The tumour suppressor C/EBPδ inhibits FBXW7 expression and promotes mammary tumour metastasis. EMBO 2010, 29:4106-4117.
44. Sudhagar S, Sathya S, Lakshmi BS. Rapid non-genomic signalling by 17β-oestradiol through c-Src involves mTOR-dependent expression of HIF-1α in breast cancer cells. Br J Cancer 2011, 105:953-960. 10.1038/bjc.2011.349, 3185958, 21897387.
45. Tang L, Ma X, Tian Q, Cheng Y, Yao H, Liu Z, Qu X, Han X. Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells. Food Chem Toxicol 2013, 56:204-213.
46. Haddadin J, Issidorides CH. The Beirut Reaction. Heterocycles 1993, 35:1503-1525.