Suppression of AKT Anti-Apoptotic Signaling by a Novel Drug Candidate Results in Growth Arrest and Apoptosis of Hepatocellular Carcinoma Cells

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Cuconati, Andrea ^a   Mills, Courtney ^a   Goddard, Cally ^a   Zhang, Xianchao ^b   Yu, Wenquan ^a,d   Guo, Haitao ^b   Xu, Xiaodong ^a,c   Block, Timothy M ^a,b  

^a BARUCH S BLUMBERG INSTITUTE   (United States)

^b DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

^c Enantigen Therapeutics Incorporated   (United States)

^d TIANJIN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINOTHIAZOLE; ANTINEOPLASTIC AGENT; CISPLATIN; DOXORUBICIN; FLUOROURACIL; HBF 0079; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN KINASE B; SORAFENIB; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER CELL CULTURE; CANCER INHIBITION; CELL CYCLE; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL VIABILITY; COLONY FORMATION; CONTROLLED STUDY; CYTOTOXICITY; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG STRUCTURE; ENZYME PHOSPHORYLATION; ENZYME REPRESSION; FEMALE; GROWTH DISORDER; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; MAXIMUM TOLERATED DOSE; MOUSE; NONHUMAN; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CARCINOMA, HEPATOCELLULAR; CELL CYCLE CHECKPOINTS; HEP G2 CELLS; HUMANS; LIVER NEOPLASMS; MICE; MULTIPROTEIN COMPLEXES; PHOSPHORYLATION; PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; THIADIAZOLES; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

MURINAE;

EID: 84872808323     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0054595     Document Type: Article

References (50)

1. Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, et al. (2008) SEER Cancer Statistics Review, 1975-2005. National Cancer Institute.
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C,et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893-2917.
3. Mathers CD, Loncar D, (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3: e442.
4. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA, (2003) The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 139: 817-823.
5. Caldwell S, Park SH, (2009) The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. J Gastroenterol 44Suppl 19: 96-101.
6. Kew M (2006) Hepatic tumors and cysts. In: Feldman M FL, Sleisenger MH, editor. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. 8th ed. Philadelphia: Saunders Elsevier.
7. El-Serag HB, Mason AC, Key C, (2001) Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 33: 62-65.
8. Thomas MB, Zhu AX, (2005) Hepatocellular carcinoma: the need for progress. J Clin Oncol 23: 2892-2899.
9. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, et al. (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390.
10. Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J, (1982) Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res 42: 3858-3863.
11. Scherer WF, Syverton JT, Gey GO, (1953) Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 97: 695-710.
12. Knowles BB, Howe CC, Aden DP, (1980) Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209: 497-499.
13. Hamilton TC, Young RC, McKoy WM, Grotzinger KR, Green JA, et al. (1983) Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res 43: 5379-5389.
14. Westley B, Rochefort H, (1979) Estradiol induced proteins in the MCF7 human breast cancer cell line. Biochem Biophys Res Commun 90: 410-416.
15. Horoszewicz JS, Leong SS, Chu TM, Wajsman ZL, Friedman M, et al. (1980) The LNCaP cell line-a new model for studies on human prostatic carcinoma. Prog Clin Biol Res 37: 115-132.
16. Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, et al. (2002) Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci U S A 99: 15655-15660.
17. Li Y, Tang ZY, Ye SL, Liu YK, Chen J, et al. (2001) Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 7: 630-636.
18. Pfeifer AM, Cole KE, Smoot DT, Weston A, Groopman JD, et al. (1993) Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens. Proc Natl Acad Sci U S A 90: 5123-5127.
19. Noguchi M, Hirohashi S, (1996) Cell lines from non-neoplastic liver and hepatocellular carcinoma tissue from a single patient. In Vitro Cell Dev Biol Anim 32: 135-137.
20. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ, (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46: 3-26.
21. Diamandis P, Wildenhain J, Clarke ID, Sacher AG, Graham J, et al. (2007) Chemical genetics reveals a complex functional ground state of neural stem cells. Nat Chem Biol 3: 268-273.
22. Lazo JS, Brady LS, Dingledine R, (2007) Building a pharmacological lexicon: small molecule discovery in academia. Mol Pharmacol 72: 1-7.
23. Weisman JL, Liou AP, Shelat AA, Cohen FE, Guy RK, et al. (2006) Searching for new antimalarial therapeutics amongst known drugs. Chem Biol Drug Des 67: 409-416.
24. Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ Jr, (2006) A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol 2: 415-416.
25. Mosmann T, (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63.
26. Kew MC, (1996) Hepatitis B and C viruses and hepatocellular carcinoma. Clin Lab Med 16: 395-406.
27. Cully M, You H, Levine AJ, Mak TW, (2006) Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6: 184-192.
28. Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, et al. (2003) Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 97: 1929-1940.
29. Nakanishi K, Sakamoto M, Yamasaki S, Todo S, Hirohashi S, (2005) Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma. Cancer 103: 307-312.
30. Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, et al. (2008) Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets 8: 27-36.
31. Chen KF, Yeh PY, Yeh KH, Lu YS, Huang SY, et al. (2008) Down-regulation of phospho-Akt is a major molecular determinant of bortezomib-induced apoptosis in hepatocellular carcinoma cells. Cancer Res 68: 6698-6707.
32. Memmott RM, Dennis PA, (2009) Akt-dependent and-independent mechanisms of mTOR regulation in cancer. Cell Signal 21: 656-664.
33. Treins C, Warne PH, Magnuson MA, Pende M, Downward J, (2010) Rictor is a novel target of p70 S6 kinase-1. Oncogene 29: 1003-1016.
34. Julien LA, Carriere A, Moreau J, Roux PP, (2010) mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol 30: 908-921.
35. Dibble CC, Asara JM, Manning BD, (2009) Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol 29: 5657-5670.
36. Tang TC, Man S, Xu P, Francia G, Hashimoto K, et al. (2010) Development of a resistance-like phenotype to sorafenib by human hepatocellular carcinoma cells is reversible and can be delayed by metronomic UFT chemotherapy. Neoplasia 12: 928-940.
37. Boyault S, Rickman DS, de Reynies A, Balabaud C, Rebouissou S, et al. (2007) Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 45: 42-52.
38. Thorgeirsson SS, Lee JS, Grisham JW, (2006) Functional genomics of hepatocellular carcinoma. Hepatology 43: S145-150.
39. Thorgeirsson SS, Grisham JW, (2002) Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31: 339-346.
40. de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, et al. (1998) Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci U S A 95: 8847-8851.
41. Buendia MA, (2000) Genetics of hepatocellular carcinoma. Semin Cancer Biol 10: 185-200.
42. Song G, Ouyang G, Bao S, (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9: 59-71.
43. Yang ZZ, Tschopp O, Baudry A, Dummler B, Hynx D, et al. (2004) Physiological functions of protein kinase B/Akt. Biochem Soc Trans 32: 350-354.
44. Fabregat I, (2009) Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol 15: 513-520.
45. Fabregat I, Roncero C, Fernandez M, (2007) Survival and apoptosis: a dysregulated balance in liver cancer. Liver Int 27: 155-162.
46. Cagatay T, Ozturk M, (2002) P53 mutation as a source of aberrant beta-catenin accumulation in cancer cells. Oncogene 21: 7971-7980.
47. Hay MP, Turcotte S, Flanagan JU, Bonnet M, Chan DA,et al. 4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient renal cell carcinoma cells by inducing autophagic cell death. J Med Chem 53: 787-797.
48. Gentles RG, Grant-Young K, Hu S, Huang Y, Poss MA, et al. (2008) Initial SAR studies on apamin-displacing 2-aminothiazole blockers of calcium-activated small conductance potassium channels. Bioorg Med Chem Lett 18: 5316-5319.
49. Ghaemmaghami S, May BC, Renslo AR, Prusiner SB, (2010) Discovery of 2-aminothiazoles as potent antiprion compounds. J Virol 84: 3408-3412.
50. Gallardo-Godoy A, Gever J, Fife KL, Silber BM, Prusiner SB, et al. (2011) 2-Aminothiazoles as therapeutic leads for prion diseases. J Med Chem 54: 1010-1021.