DC120, a novel AKT inhibitor, preferentially suppresses nasopharyngeal carcinoma cancer stem-like cells by downregulating Sox2

Oncotarget

Volumn 6, Issue 9, 2015, Pages 6944-6958

  Qin, Juan ^a   Ji, Jiao ^a   Deng, Rong ^a   Tang, Jun ^a,b   Yang, Fen ^a   Feng, Gong Kan ^a   Chen, Wen Dan ^a   Wu, Xiao Qi ^a   Qian, Xiao Jun ^a   Ding, Ke ^c,d   Zhu, Xiao Feng ^a  

^a SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^b SUN YAT SEN UNIVERSITY   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^d GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH   (China)

Author keywords

Cancer stem like cells; DC120; Nasopharyngeal carcinoma; PKB AKT

Indexed keywords

CISPLATIN; DC 120; GLYCOGEN SYNTHASE KINASE 3BETA; MESSENGER RNA; MICRORNA; MICRORNA 30A; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE B INHIBITOR; PROTEIN P27; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR SOX2; UNCLASSIFIED DRUG; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; GLYCOGEN SYNTHASE KINASE 3; GSK3B PROTEIN, HUMAN; GSK3B PROTEIN, MOUSE; N-(1-AMINO-3-(2,4-DICHLOROPHENYL)PROPAN-2-YL)-2-(2-(METHYLAMINO)PYRIMIDIN-4-YL)THIAZOLE-5-CARBOXAMIDE; PYRIMIDINE DERIVATIVE; SOX2 PROTEIN, HUMAN; THIAZOLE DERIVATIVE; TRANSCRIPTION FACTOR SOX;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER RECURRENCE; CELL FRACTIONATION; CELL RENEWAL; CHEMICAL PHENOMENA; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; DRUG POTENTIATION; GENE EXPRESSION REGULATION; GENE SILENCING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MONOTHERAPY; MOUSE; NASOPHARYNX CARCINOMA; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIDE POPULATION CELL; SIGNAL TRANSDUCTION; SOX2 GENE; SPHERE FORMATION; TUMOR RECURRENCE; TUMOR VOLUME; TUMOR XENOGRAFT; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BINDING SITE; CANCER STEM CELL; CELL SEPARATION; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; ENZYMOLOGY; FLOW CYTOMETRY; IC50; METABOLISM; NASOPHARYNX TUMOR; PHOSPHORYLATION; SCID MOUSE;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; CELL SEPARATION; DOWN-REGULATION; FLOW CYTOMETRY; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 BETA; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MICE, SCID; NASOPHARYNGEAL NEOPLASMS; NEOPLASM RECURRENCE, LOCAL; NEOPLASTIC STEM CELLS; PHENOTYPE; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; PYRIMIDINES; SOXB1 TRANSCRIPTION FACTORS; THIAZOLES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84927126692     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.3128     Document Type: Article

References (57)

1. Tao Q, Chan AT. Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert reviews in molecular medicine. 2007; 9:1-24.
2. Hui EP, Leung SF, Au JS, Zee B, Tung S, Chua D, Sze WM, Law CK, Leung TW, Chan AT. Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Cancer. 2004; 101:300-306.
3. Richardson PG, Wolf J, Jakubowiak A, Zonder J, Lonial S, Irwin D, Densmore J, Krishnan A, Raje N, Bar M, Martin T, Schlossman R, Ghobrial IM, Munshi N, Laubach J, Allerton J, et al. Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2011; 29:4243-4249.
4. Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, Margolick JB, Liotta LA, Petricoin E 3rd, Zhang Y. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104:16158-16163.
5. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414:105-111.
6. Bellacosa A, Kumar CC, Di Cristofano A, Testa JR. Activation of AKT kinases in cancer: implications for therapeutic targeting. Advances in cancer research. 2005; 94:29-86.
7. Deng R, Tang J, Ma JG, Chen SP, Xia LP, Zhou WJ, Li DD, Feng GK, Zeng YX, Zhu XF. PKB/Akt promotes DSB repair in cancer cells through upregulating Mre11 expression following ionizing radiation. Oncogene. 2011; 30:944-955.
8. Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nature reviews Clinical oncology. 2011; 8:528-539.
9. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007; 129:1261-1274.
10. Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y, Maehara Y. Deregulation of the Akt pathway in human cancer. Current cancer drug targets. 2008; 8:27-36.
11. Kalinsky K, Heguy A, Bhanot UK, Patil S, Moynahan ME. PIK3CA mutations rarely demonstrate genotypic intratumoral heterogeneity and are selected for in breast cancer progression. Breast cancer research and treatment. 2011; 129:635-643.
12. Whitehall VL, Rickman C, Bond CE, Ramsnes I, Greco SA, Umapathy A, McKeone D, Faleiro RJ, Buttenshaw RL, Worthley DL, Nayler S, Zhao ZZ, Montgomery GW, Mallitt KA, Jass JR, Matsubara N, et al. Oncogenic PIK3CA mutations in colorectal cancers and polyps. International journal of cancer Journal international du cancer. 2012; 131:813-820.
13. Li H, Gao Q, Guo L, Lu SH. The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells. Cancer biology & therapy. 2011; 11:950-958.
14. Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, Holland EC. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell stem cell. 2009; 4:226-235.
15. Singh S, Trevino J, Bora-Singhal N, Coppola D, Haura E, Altiok S, Chellappan SP. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer. Molecular cancer. 2012; 11:73.
16. Imai Y, Yoshimori M, Fukuda K, Yamagishi H, Ueda Y. The PI3K/Akt inhibitor LY294002 reverses BCRP-mediated drug resistance without affecting BCRP translocation. Oncology reports. 2012; 27:1703-1709.
17. Chatterjee A, Chatterjee U, Ghosh MK. Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: implications in human prostate cancer. Cell death & disease. 2013; 4:e543.
18. Cheng Y, Cheung AK, Ko JM, Phoon YP, Chiu PM, Lo PH, Waterman ML, Lung ML. Physiological beta-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinoma. BMC Cell Biol. 2013; 14:44.
19. Hers I, Vincent EE, Tavare JM. Akt signalling in health and disease. Cellular signalling. 2011; 23:1515-1527.
20. Deng R, Yang F, Chang SH, Tang J, Qin J, Feng GK, Ding K, Zhu XF. DC120, a novel and potent inhibitor of AKT kinase, induces tumor cell apoptosis and suppresses tumor growth. Molecular pharmacology. 2012; 82:189-198.
21. Yang F, Deng R, Qian XJ, Chang SH, Wu XQ, Qin J, Feng GK, Ding K, Zhu XF. Feedback loops blockade potentiates apoptosis induction and antitumor activity of a novel AKT inhibitor DC120 in human liver cancer. Cell death & disease. 2014; 5:e1114.
22. Wu MS, Wang GF, Zhao ZQ, Liang Y, Wang HB, Wu MY, Min P, Chen LZ, Feng QS, Bei JX, Zeng YX, Yang D. Smac mimetics in combination with TRAIL selectively target cancer stem cells in nasopharyngeal carcinoma. Molecular cancer therapeutics. 2013; 12:1728-1737.
23. Firat E, Weyerbrock A, Gaedicke S, Grosu AL, Niedermann G. Chloroquine or chloroquine-PI3K/Akt pathway inhibitor combinations strongly promote gamma-irradiation-induced cell death in primary stem-like glioma cells. PloS one. 2012; 7:e47357.
24. McAuliffe SM, Morgan SL, Wyant GA, Tran LT, Muto KW, Chen YS, Chin KT, Partridge JC, Poole BB, Cheng KH, Daggett J Jr., Cullen K, Kantoff E, Hasselbatt K, Berkowitz J, Muto MG, et al. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109:E2939-2948.
25. Liang J, Zubovitz J, Petrocelli T, Kotchetkov R, Connor MK, Han K, Lee JH, Ciarallo S, Catzavelos C, Beniston R, Franssen E, Slingerland JM. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nature medicine. 2002; 8:1153-1160.
26. Narita Y, Nagane M, Mishima K, Huang HJ, Furnari FB, Cavenee WK. Mutant epidermal growth factor receptor signaling down-regulates p27 through activation of the phosphatidylinositol 3-kinase/Akt pathway in glioblastomas. Cancer research. 2002; 62:6764-6769.
27. Li H, Collado M, Villasante A, Matheu A, Lynch CJ, Canamero M, Rizzoti K, Carneiro C, Martinez G, Vidal A, Lovell-Badge R, Serrano M. p27(Kip1) directly represses Sox2 during embryonic stem cell differentiation. Cell stem cell. 2012; 11:845-852.
28. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136:215-233.
29. Liu K, Lin B, Zhao M, Yang X, Chen M, Gao A, Liu F, Que J, Lan X. The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cellular signalling. 2013; 25:1264-1271.
30. Trohatou O, Zagoura D, Bitsika V, Pappa KI, Antsaklis A, Anagnou NP, Roubelakis MG. Sox2 suppression by miR-21 governs human mesenchymal stem cell properties. Stem cells translational medicine. 2014; 3:54-68.
31. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer research. 2003; 63:5821-5828.
32. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133:704-715.
33. Marotta LL, Polyak K. Cancer stem cells: a model in the making. Current opinion in genetics & development. 2009; 19:44-50.
34. Blagosklonny MV. Cancer stem cell and cancer stemloids: from biology to therapy. Cancer biology & therapy. 2007; 6:1684-1690.
35. Francipane MG, Lagasse E. Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1. Oncotarget. 2013; 4:1948-1962.
36. Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG, Wicha MS. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS biology. 2009; 7:e1000121.
37. Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH. Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer research. 2007; 67:3716-3724.
38. Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, Schultz PG, Reddy VA. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106:268-273.
39. Hambardzumyan D, Becher OJ, Rosenblum MK, Pandolfi PP, Manova-Todorova K, Holland EC. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes & development. 2008; 22:436-448.
40. Yang X, Fraser M, Moll UM, Basak A, Tsang BK. Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway. Cancer research. 2006; 66:3126-3136.
41. Yang F, Qian XJ, Qin W, Deng R, Wu XQ, Qin J, Feng GK, Zhu XF. Dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 has a therapeutic potential and sensitizes cisplatin in nasopharyngeal carcinoma. PloS one. 2013; 8:e59879.
42. Chan KC, Ting CM, Chan PS, Lo MC, Lo KW, Curry JE, Smyth T, Lee AW, Ng WT, Tsao GS, Wong RN, Lung ML, Mak NK. A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation. Molecular cancer. 2013; 12:128.
43. Ormsbee Golden BD, Wuebben EL, Rizzino A. Sox2 expression is regulated by a negative feedback loop in embryonic stem cells that involves AKT signaling and FoxO1. PloS one. 2013; 8:e76345.
44. Jeon HM, Sohn YW, Oh SY, Kim SH, Beck S, Kim S, Kim H. ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer research. 2011; 71:3410-3421.
45. Bourguignon LY, Wong G, Earle C, Chen L. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. The Journal of biological chemistry. 2012; 287:32800-32824.
46. Schneider L, Pellegatta S, Favaro R, Pisati F, Roncaglia P, Testa G, Nicolis SK, Finocchiaro G F. DNA Damage in Mammalian Neural Stem Cells Leads to Astrocytic Differentiation Mediated by BMP2 Signaling through JAK-STAT. Stem cell reports. 2013; 1:123-138.
47. Lun SW, Cheung ST, Cheung PF, To KF, Woo JK, Choy KW, Chow C, Cheung CC, Chung GT, Cheng AS, Ko CW, Tsao SW, Busson P, Ng MH, Lo KW. CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma. PloS one. 2012; 7:e52426.
48. Boumahdi S, Driessens G, Lapouge G, Rorive S, Nassar D, Le Mercier M, Delatte B, Caauwe A, Lenglez S, Nkusi E, Brohee S, Salmon I, Dubois C, del Marmol V, Fuks F, Beck B, et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature. 2014; 511:246-250.
49. Yang HJ, Huang TJ, Yang CF, Peng LX, Liu RY, Yang GD, Chu QQ, Huang JL, Liu N, Huang HB, Zhu ZY, Qian CN, Huang BJ. Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells. Virol J. 2013; 10:314.
50. Yu X, Zhen Y, Yang H, Wang H, Zhou Y, Wang E, Marincola FM, Mai C, Chen Y, Wei H, Song Y, Lyu X, Ye Y, Cai L, Wu Q, Zhao M, et al. Loss of connective tissue growth factor as an unfavorable prognosis factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell growth in nasopharyngeal carcinoma. Cell death & disease. 2013; 4:e634.
51. Yu L, Lu J, Zhang B, Liu X, Wang L, Li SY, Peng XH, Xu X, Tian WD, Li XP. miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2. Oncology letters. 2013; 5:1223-1228.
52. Vimalraj S, Miranda PJ, Ramyakrishna B, Selvamurugan N. Regulation of breast cancer and bone metastasis by microRNAs. Disease markers. 2013; 35:369-387.
53. Wu Z, Wu Y, Tian Y, Sun X, Liu J, Ren H, Liang C, Song L, Hu H, Wang L, Jiao B. Differential effects of miR-34c-3p and miR-34c-5p on the proliferation, apoptosis and invasion of glioma cells. Oncology letters. 2013; 6:1447-1452.
54. Wu C, Jin B, Chen L, Zhuo D, Zhang Z, Gong K, Mao Z. MiR-30d induces apoptosis and is regulated by the Akt/FOXO pathway in renal cell carcinoma. Cellular signalling. 2013; 25:1212-1221.
55. Qian CN, Berghuis B, Tsarfaty G, Bruch M, Kort EJ, Ditlev J, Tsarfaty I, Hudson E, Jackson DG, Petillo D, Chen J, Resau JH, Teh BT. Preparing the "soil": the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer research. 2006; 66:10365-10376.
56. Deng R, Tang J, Xia LP, Li DD, Zhou WJ, Wang LL, Feng GK, Zeng YX, Gao YH, Zhu XF. ExcisaninA, a diterpenoid compound purified from Isodon MacrocalyxinD, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of its signal pathway. Molecular cancer therapeutics. 2009; 8:873-882.
57. Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR. A viral microRNA functions as an orthologue of cellular miR-155. Nature. 2007; 450:1096-1099.