Synergistic anticancer activity of HS-173, a novel PI3K inhibitor in combination with Sorafenib against pancreatic cancer cells

Cancer Letters

Volumn 331, Issue 2, 2013, Pages 250-261

  Yun, Sun Mi ^a   Jung, Kyung Hee ^a   Lee, Hyunseung ^a   Son, Mi Kwon ^a   Seo, Ju Hyeon ^a   Yan, Hong Hua ^a   Park, Byung Hee ^a   Hong, Sungwoo ^b   Hong, Soon Sun ^a  

^a Inha University School of Medicine   (South Korea)

^b Korea Advanced Institute of Science and Technology (KAIST)   (South Korea)

Author keywords

Pancreatic cancer; PI3K AKT; RAF MAPK; Sorafenib

Indexed keywords

CASPASE 3; CD31 ANTIGEN; ETHYL 6 [5 (PHENYLSULFONAMIDO)PYRIDIN 3 YL]IMIDAZO[1,2 A]PYRIDINE 3 CARBOXYLATE; HS 173; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MITOGEN ACTIVATED PROTEIN KINASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; RAF PROTEIN; SORAFENIB; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENTIATION; DRUG STRUCTURE; HUMAN; HUMAN CELL; MALE; MITOCHONDRIAL MEMBRANE POTENTIAL; MOUSE; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; UMBILICAL VEIN ENDOTHELIAL CELL;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOTTING, WESTERN; CELL LINE, TUMOR; DRUG SYNERGISM; ENZYME INHIBITORS; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IN SITU NICK-END LABELING; MALE; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICE; MICE, INBRED BALB C; NIACINAMIDE; PANCREATIC NEOPLASMS; PHENYLUREA COMPOUNDS; PHOSPHATIDYLINOSITOL 3-KINASES; PYRIDINES; SULFONAMIDES;

MUS;

EID: 84875363717     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2013.01.007     Document Type: Article

References (46)

1. Jemal A., Siegel R., Ward E., Hao Y., Xu J., Murray T., Thun M.J. Cancer statistics. CA Cancer J. Clin. 2008, 58:71-96.
2. Jemal A., Siegel R., Xu J., Ward E. Cancer statistics. CA Cancer J. Clin. 2010, 60:277-300.
3. Burris H.A., Moore M.J., Andersen J., Green M.R., Rothenberg M.L., Modiano M.R., Cripps M.C., Portenoy R.K., Storniolo A.M., Tarassoff P., Nelson R., Dorr F.A., Stephens C.D., Von Hoff D.D. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 1997, 15:2403-2413.
4. Motojima K., Urano T., Nagata Y., Shiku H., Tsurifune T., Kanematsu T. Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma. Ann. Surg. 1993, 217:138-143.
5. Ishimura N., Yamasawa K., Karim Rumi M.A., Kadowaki Y., Ishihara S., Amano Y., Nio Y., Higami T., Kinoshita Y. BRAF and K-ras gene mutations in human pancreatic cancers. Cancer Lett. 2003, 199:169-173.
6. Dent P., Yacoub A., Fisher P.B., Hagan M.P., Grant S. MAPK pathways in radiation responses. Oncogene 2003, 22:5885-5896.
7. Keen R.R., Stella L., Flanigan D.P., Lands W.E. Differential detection of plasma hydroperoxides in sepsis. Crit. Care Med. 1991, 19:1114-1119.
8. Campbell P.M., Der C.J. Oncogenic Ras and its role in tumor cell invasion and metastasis. Semin. Cancer Biol. 2004, 14:105-114.
9. Davies B.R., Logie A., McKay J.S., Martin P., Steele S., Jenkins R., Cockerill M., Cartlidge S., Smith P.D. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 2007, 6:2209-2219.
10. Wilhelm S.M., Carter C., Tang L., Wilkie D., McNabola A., Rong H., Chen C., Zhang X., Vincent P., McHugh M., Cao Y., Shujath J., Gawlak S., Eveleigh D., Rowley B., Liu L., Adnane L., Lynch M., Auclair D., Taylor I., Gedrich R., Voznesensky A., Riedl B., Post L.E., Bollag G., Trail P.A. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004, 64:7099-7109.
11. Wilhelm S.M., Adnane L., Newell P., Villanueva A., Llovet J.M., Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol. Cancer Ther. 2008, 7:3129-3140.
12. Flaherty K.T. Sorafenib: delivering a targeted drug to the right targets. Expert Rev. Anticancer Ther. 2007, 7:617-626.
13. Burris H., Rocha-Lima C. New therapeutic directions for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways. Oncologist 2008, 13:289-298.
14. Siu L.L., Awada A., Takimoto C.H., Piccart M., Schwartz B., Giannaris T., Lathia C., Petrenciuc O., Moore M.J. Phase I trial of Sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin. Cancer Res. 2006, 12:144-151.
15. Ruggeri B.A., Huang L., Wood M., Cheng J.Q., Testa J.R. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol. Carcinog. 1998, 21:81-86.
16. Rettig R.A. The media and health. Essay review. J. Health Polit. Policy Law 1992, 17:575-583.
17. Campbell P.M., Groehler A.L., Lee K.M., Ouellette M.M., Khazak V., Der C.J. K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. Cancer Res. 2007, 67:2098-2106.
18. Zhao J.J., Cheng H., Jia S., Wang L., Gjoerup O.V., Mikami A., Roberts T.M. The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc. Natl. Acad. Sci. USA 2006, 103:16296-16300.
19. Gupta S., Ramjaun A.R., Haiko P., Wang Y., Warne P.H., Nicke B., Nye E., Stamp G., Alitalo K., Downward J. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell 2007, 129:957-968.
20. Campbell M., Allen W.E., Sawyer C., Vanhaesebroeck B., Trimble E.R. Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathways. Circ. Res. 2004, 95:380-388.
21. Naegele S., Morley S.J. Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress. J. Biol. Chem. 2004, 279:46023-46034.
22. Lasithiotakis K.G., Sinnberg T.W., Schittek B., Flaherty K.T., Kulms D., Maczey E., Garbe C., Meier F.E. Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells. J Invest Dermatol 2008, 128:2013-2023.
23. Newell P., Toffanin S., Villanueva A., Chiang D.Y., Minguez B., Cabellos L., Savic R., Hoshida Y., Lim K.H., Melgar-Lesmes P., Yea S., Peix J., Deniz K., Fiel M.I., Thung S., Alsinet C., Tovar V., Mazzaferro V., Bruix J., Roayaie S., Schwartz M., Friedman S.L., Llovet J.M. Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined Sorafenib and rapamycin in vivo. J. Hepatol. 2009, 51:725-733.
24. Engelman J.A., Chen L., Tan X., Crosby K., Guimaraes A.R., Upadhyay R., Maira M., McNamara K., Perera S.A., Song Y., Chirieac L.R., Kaur R., Lightbown A., Simendinger J., Li T., Padera R.F., Garcia-Echeverria C., Weissleder R., Mahmood U., Cantley L.C., Wong K.K. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med. 2008, 14:1351-1356.
25. Halilovic E., She Q.B., Ye Q., Pagliarini R., Sellers W.R., Solit D.B., Rosen N. PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling. Cancer Res. 2010, 70:6804-6814.
26. Lee H., Jung K.H., Jeong Y., Hong S., Hong S.S. HS-173, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, has anti-tumor activity through promoting apoptosis and inhibiting angiogenesis. Cancer Lett. 2013, 328:152-159.
27. Kim O., Jeong Y., Lee H., Hong S.S., Hong S. Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis. J. Med. Chem. 2011, 54:2455-2466.
28. Hausenloy D.J., Mocanu M.M., Yellon D.M. Cross-talk between the survival kinases during early reperfusion: its contribution to ischemic preconditioning. Cardiovasc. Res. 2004, 63:305-312.
29. Almoguera C., Shibata D., Forrester K., Martin J., Arnheim N., Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988, 53:549-554.
30. Young A., Lyons J., Miller A.L., Phan V.T., Alarcon I.R., McCormick F. Ras signaling and therapies. Adv. Cancer Res. 2009, 102:1-17.
31. D.J. Burgess, Therapeutics: Keeping one step ahead. Nat. Rev. Cancer 12 (2012) 82-83.
32. Schlieman M.G., Fahy B.N., Ramsamooj R., Beckett L., Bold R.J. Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br. J. Cancer 2003, 89:2110-2115.
33. Edling C.E., Selvaggi F., Buus R., Maffucci T., Di Sebastiano P., Friess H., Innocenti P., Kocher H.M., Falasca M. Key role of phosphoinositide 3-kinase class IB in pancreatic cancer. Clin. Cancer Res. 2010, 16:4928-4937.
34. Carracedo A., Ma L., Teruya-Feldstein J., Rojo F., Salmena L., Alimonti A., Egia A., Sasaki A.T., Thomas G., Kozma S.C., Papa A., Nardella C., Cantley L.C., Baselga J., Pandolfi P.P. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J. Clin. Invest. 2008, 118:3065-3074.
35. Reni M., Balzano G., Aprile G., Cereda S., Passoni P., Zerbi A., Tronconi M.C., Milandri C., Saletti P., Rognone A., Fugazza C., Magli A., Di Muzio N., Di Carlo V., Villa E. Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. Ann. Surg. Oncol. 2012, 19:2256-2263.
36. Philip P.A., Benedetti J., Corless C.L., Wong R., O'Reilly E.M., Flynn P.J., Rowland K.M., Atkins J.N., Mirtsching B.C., Rivkin S.E., Khorana A.A., Goldman B., Fenoglio-Preiser C.M., Abbruzzese J.L., Blanke C.D. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J. Clin. Oncol. 2010, 28:3605-3610.
37. Kindler H.L., Niedzwiecki D., Hollis D., Sutherland S., Schrag D., Hurwitz H., Innocenti F., Mulcahy M.F., O'Reilly E., Wozniak T.F., Picus J., Bhargava P., Mayer R.J., Schilsky R.L., Goldberg R.M. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol. 2010, 28:3617-3622.
38. Hofmann I., Weiss A., Elain G., Schwaederle M., Sterker D., Romanet V., Schmelzle T., Lai A., Brachmann S.M., Bentires-Alj M., Roberts T.M., Sellers W.R., Hofmann F., Maira S.M. K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo. PLoS ONE 2012, 7:e44146.
39. Kuznetsov A.V., Usson Y., Leverve X., Margreiter R. Subcellular heterogeneity of mitochondrial function and dysfunction: evidence obtained by confocal imaging. Mol. Cell. Biochem. 2004, 256-257:359-365.
40. Petronilli V., Penzo D., Scorrano L., Bernardi P., Di Lisa F. The mitochondrial permeability transition, release of cytochrome c and cell death. J. Biol. Chem. 2001, 276:12030-12034.
41. Armstrong J.S. Mitochondria: a target for cancer therapy. Br. J. Pharmacol. 2006, 147:239-248.
42. Sos M.L., Fischer S., Ullrich R., Peifer M., Heuckmann J.M., Koker M., Heynck S., Stuckrath I., Weiss J., Fischer F., Michel K., Goel A., Regales L., Politi K.A., Perera S., Getlik M., Heukamp L.C., Ansen S., Zander T., Beroukhim R., Kashkar H., Shokat K.M., Sellers W.R., Rauh D., Orr C., Hoeflich K.P., Friedman L., Wong K.K., Pao W., Thomas R.K. Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer. Proc. Natl. Acad. Sci. USA 2009, 106:18351-18356.
43. Hoeflich K.P., O'Brien C., Boyd Z., Cavet G., Guerrero S., Jung K., Januario T., Savage H., Punnoose E., Truong T., Zhou W., Berry L., Murray L., Amler L., Belvin M., Friedman L.S., Lackner M.R. In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin. Cancer Res. 2009, 15:4649-4664.
44. Folkman J. Angiogenesis. Annu. Rev. Med. 2006, 57:1-18.
45. Blood C.H., Zetter B.R. Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim. Biophys. Acta 1990, 1032:89-118.
46. Carmeliet P. Angiogenesis in health and disease. Nat. Med. 2003, 9:653-660.