A novel imidazopyridine derivative, HS-106, induces apoptosis of breast cancer cells and represses angiogenesis by targeting the PI3K/mTOR pathway

Cancer Letters

Volumn 329, Issue 1, 2013, Pages 59-67

  Li, Guang Yong ^a,b   Jung, Kyung Hee ^a   Lee, Hyunseung ^a   Son, Mi Kwon ^a   Seo, JuHyeon ^a   Hong, Sang Won ^a   Jeong, Yujeong ^c   Hong, Sungwoo ^c   Hong, Soon Sun ^a  

^a Inha University School of Medicine   (South Korea)

^b LIAOCHENG UNIVERSITY   (China)

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

Author keywords

Angiogenesis; Apoptosis; Breast cancer; MTOR; PI3K

Indexed keywords

ANGIOGENESIS INHIBITOR; CASPASE 3; CYCLIN B1; HS 106; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MAMMALIAN TARGET OF RAPAMYCIN; N [5 (3 CYANOIMIDAZO[1,2 A]PYRIDIN 6 YL)PYRIDIN 3 YL]BENZENESULFONAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN TYROSINE PHOSPHATASE; UNCLASSIFIED DRUG;

ANTIANGIOGENIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CELL PROLIFERATION; CELL VIABILITY; CHROMATIN CONDENSATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVITY; ENZYME MODIFICATION; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; IN VIVO STUDY; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; UMBILICAL VEIN ENDOTHELIAL CELL; UPREGULATION;

ANGIOGENESIS INHIBITORS; ANIMALS; APOPTOSIS; BREAST NEOPLASMS; CARCINOGENICITY TESTS; CELL LINE, TUMOR; CYCLIN B1; FEMALE; G2 PHASE CELL CYCLE CHECKPOINTS; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IMIDAZOLES; MALE; MICE; MICE, INBRED BALB C; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHATIDYLINOSITOL 3-KINASE; PYRIDINES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84871714394     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2012.10.013     Document Type: Article

References (38)

1. Jemal A., Siegel R., Xu J., Ward E. Cancer statistics. Cancer J. Clin. 2010, 60(2010):277-300.
2. Courtney K.D., Corcoran R.B., Engelman J.A. The PI3K pathway as drug target in human cancer. J. Clin. Oncol. 2010, 28:1075-1083.
3. Woodgett J.R. Recent advances in the protein kinase B signaling pathway. Curr. Opin. Cell Biol. 2005, 17:150-157.
4. Frias M.A., Thoreen C.C., Jaffe J.D., Schroder W., Sculley T., Carr S.A., Sabatini D.M. MSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr. Biol. 2006, 16:1865-1870.
5. Guertin D.A., Stevens D.M., Thoreen C.C., Burds A.A., Kalaany N.Y., Moffat J., Brown M., Fitzgerald K.J., Sabatini D.M. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev. Cell 2006, 11:859-871.
6. Jacinto E., Facchinetti V., Liu D., Soto N., Wei S., Jung S.Y., Huang Q., Qin J., Su B. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 2006, 127:125-137.
7. Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307:1098-1101.
8. Yang Q., Inoki K., Ikenoue T., Guan K.L. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes. Dev. 2006, 20:2820-2832.
9. Manning B.D., Cantley L.C. AKT/PKB signaling: navigating downstream. Cell 2007, 129:1261-1274.
10. Calleja V., Alcor D., Laguerre M., Park J., Vojnovic B., Hemmings B.A., Downward J., Parker P.J., Larijani B. Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo. PLoS Biol. 2007, 5:e95.
11. Easton J.B., Houghton P.J. MTOR and cancer therapy. Oncogene 2006, 25:6436-6446.
12. Vogelstein B., Kinzler K.W. Cancer genes and the pathways they control. Nat. Med. 2004, 10:789-799.
13. Yap T.A., Garrett M.D., Walton M.I., Raynaud F., de Bono J.S., Workman P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr. Opin. Pharmacol. 2008, 8:393-412.
14. Garcia-Echeverria C., Sellers W.R. Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene 2008, 27:5511-5526.
15. Lu Y., Wang H., Mills G.B. Targeting PI3K-AKT pathway for cancer therapy. Rev. Clin. Exp. Hematol. 2003, 7:205-228.
16. Fresno Vara J.A., Casado E., de Castro J., Cejas P., Belda-Iniesta C., Gonzalez-Baron M. PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev. 2004, 30:193-204.
17. 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.
18. McAuliffe P.F., Meric-Bernstam F., Mills G.B., Gonzalez-Angulo A.M. Deciphering the Role of PI3K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin. Breast Cancer 2010, 10:S59-65.
19. Weinstein I.B., Joe A.K. Mechanisms of disease: oncogene addiction - a rationale for molecular targeting in cancer therapy. Nat. Clin. Pract. Oncol. 2006, 3:448-457.
20. Kuo K.T., Mao T.L., Jones S., Veras E., Ayhan A., Wang T.L., Glas R., Slamon D., Velculescu V.E., Kuman R.J., Shih Ie M. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am. J. Pathol. 2009, 174:1597-1601.
21. Lee J.W., Soung Y.H., Kim S.Y., Lee H.W., Park W.S., Nam S.W., Kim S.H., Lee J.Y., Yoo N.J., Lee S.H. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 2005, 24:1477-1480.
22. Levine D.A., Bogomolniy F., Yee C.J., Lash A., Barakat R.R., Borgen P.I., Boyd J. Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin. Cancer Res. 2005, 11:2875-2878.
23. Dowling R.J., Topisirovic I., Alain T., Bidinosti M., Fonseca B.D., Petroulakis E., Wang X., Larsson O., Selvaraj A., Liu Y., Kozma S.C., Thomas G., Sonenberg N. MTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 2010, 328:1172-1176.
24. Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998, 17:1371-1384.
25. Liang J., Slingerland J.M. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle 2003, 2:339-345.
26. Hirose Y., Katayama M., Mirzoeva O.K., Berger M.S., Pieper R.O. Akt activation suppresses Chk2-mediated, methylating agent-induced G2 arrest and protects from temozolomide-induced mitotic catastrophe and cellular senescence. Cancer Res. 2005, 65:4861-4869.
27. Sanchez Y., Wong C., Thoma R.S., Richman R., Wu Z., Piwnica-Worms H., Elledge S.J. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 1997, 277:1497-1501.
28. Franke T.F., Hornik C.P., Segev L., Shostak G.A., Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene 2003, 22:8983-8998.
29. Serra V., Markman B., Scaltriti M., Eichhorn P.J., Valero V., Guzman M., Botero M.L., Llonch E., Atzori F., Di Cosimo S., Maira M., Garcia-Echeverria C., Parra J.L., Arribas J., Baselga J. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res. 2008, 68:8022-8030.
30. Zha J., Harada H., Yang E., Jockel J., Korsmeyer S.J. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 1996, 87:619-628.
31. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell 2000, 100:57-70.
32. Folkman J. Angiogenesis. Ann. Rev. Med. 2006, 57:1-18.
33. Graupera M., Guillermet-Guibert J., Foukas L.C., Phng L.K., Cain R.J., Salpekar A., Pearce W., Meek S., Millan J., Cutillas P.R., Smith A.J., Ridley A.J., Ruhrberg C., Gerhardt H., Vanhaesebroeck B. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature 2008, 453:662-666.
34. Huang S., Houghton P.J. Targeting mTOR signaling for cancer therapy. Curr. Opin. Pharmacol. 2003, 3:371-377.
35. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 2003, 3:721-732.
36. Hellwig-Burgel T., Stiehl D.P., Wagner A.E., Metzen E., Jelkmann W. Review: hypoxia-inducible factor-1 (HIF-1): a novel transcription factor in immune reactions. J. Interferon Cytokine Res. 2005, 25:297-310.
37. Fang J., Ding M., Yang L., Liu L.Z., Jiang B.H. PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis. Cell Signal 2007, 19:2487-2497.
38. Blood C.H., Zetter B.R. Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim. Biophys. Acta 1990, 1032:89-118.