Antiproliferative activity of PEP005, a novel ingenol angelate that modulates PKC functions, alone and in combination with cytotoxic agents in human colon cancer cells

British Journal of Cancer

Volumn 99, Issue 11, 2008, Pages 1808-1815

  Benhadji, K A ^a,b   Serova, M ^a   Ghoul, A ^a,b   Cvitkovic, E ^a   Le Tourneau, C ^a   Ogbourne, S M ^c   Lokiec, F ^b   Calvo, F ^d   Hammel, P ^a   Faivre, S ^a   Raymond, E ^a  

^a BEAUJON HOSPITAL   (France)

^b Cancer Research Center Rene Huguenin   (France)

^c Peplin Ltd   (Australia)

^d SAINT LOUIS HOSPITAL   (France)

Author keywords

Drug resistance; P38; PKC ; PKC ; Schedule dependency

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; ANTINEOPLASTIC AGENT; CISPLATIN; DOCETAXEL; DOXORUBICIN; FLUOROURACIL; GEMCITABINE; MITOGEN ACTIVATED PROTEIN KINASE P38; NAVELBINE; OXALIPLATIN; PEP 005; PROTEIN KINASE C DELTA; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL CYCLE G1 PHASE; COLON CANCER; COLORECTAL CANCER; CYTOTOXICITY; DRUG ANTAGONISM; DRUG POTENTIATION; HUMAN; HUMAN CELL; IC 50; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SOLID TUMOR;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BLOTTING, WESTERN; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; COLONIC NEOPLASMS; DITERPENES; ESTERS; HUMANS; INHIBITORY CONCENTRATION 50; ISOENZYMES; PROTEIN KINASE C;

EID: 56749156358     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/sj.bjc.6604642     Document Type: Article

References (24)

1. Blass M, Kronfeld I, Kazimirsky G, Blumberg PM, Brodie C (2002) Tyrosine phosphorylation of protein kinase Cδ is essential for its apoptotic effect in response to etoposide. Mol Cell Biol 22: 182-195
2. Chou TC, Talalay P (1984) Quantitive analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enz Regul 22: 27-55
3. Cozzi SJ, Parsons PG, Ogbourne SM, Pedley J, Boyle GM (2006) Induction of senescence in diterpene ester-treated melanoma cells via protein kinase C-dependent hyperactivation of the mitogen-activated protein kinase pathway. Cancer Res 66: 10083-10091
4. Emoto Y, Kisaki H, Manome Y, Kharbanda S, Kufe D (1996) Activation of protein kinase Cdelta in human myeloid leukemia cells treated with 1-beta-D-arabinofuranosylcytosine. Blood 87: 1990-1996
5. Ghoul A, Serova M, Benhadji KA, Cvitkovic E, Faivre S, Philips E, Calvo F, Lokiec F, Raymond E (2005) Protein Kinase C α and δ are members of a large kinase family of high potential for novel anticancer targeted therapy. Targeted Oncol 1: 34-47
6. Gillespie SK, Zhang XD, Hersey P (2004) Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in melanoma cells. Mol Cancer Ther 12: 1651-1658
7. Griner EM, Kazanietz MG (2007) Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer 7: 281-294
8. Hampson P, Chahal H, Khanim F, Hayden R, Mulder A, Assi LK, Bunce CM, Lord JM (2005) PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC. Blood 106: 1362-1368
9. Hansen M, Nielsen S, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119: 203-210
10. Humphries MJ, Limesand KH, Schneider JC, Nakayama KI, Anderson SM, Reyland ME (2006) Suppression of apoptosis in the protein kinase C delta null mouse in vivo. J Biol Chem 281: 9728-9737
11. Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64: 3243-3255
12. Koutcher JA, Motwani M, Zakian KL, Li XK, Matei C, Dyke JP, Ballon D, Yoo HH, Schwartz GK (2000) The in vivo effect of bryostatin-1 on paclitaxel-induced tumor growth, mitotic entry, and blood flow. Clin Cancer Res 6: 1498-1507
13. Ma S, Rosen ST (2007) Enzastaurin. Curr Opin Oncol 19: 590-595
14. Mackay HJ, Twelves CJ (2007) Targeting the protein kinase C family: are we there yet? Nat Rev Cancer 7: 554-562
15. Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG (2004) Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 64: 2833-2839
16. Paz-Ares L, Douillard JY, Koralewski P, Manegold C, Smit EF, Reyes JM, Chang GC, John WJ, Peterson PM, Obasaju CK, Lahn M, Gandara DR (2006) Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-α antisense oligonucleotide, in patients with advanced stage non-small-cell lung cancer. J Clin Oncol 24: 1428-1434
17. Persaud SD, Hoang V, Huang J, Basu A (2005) Involvement of proteolytic activation of PKCdelta in cisplatin-induced apoptosis in human small cell lung cancer H69 cells. Int J Oncol 27: 149-154
18. Pongracz J, Clark P, Neoptolemos JP, Lord JM (1995) Expression of protein-kinase-C isoenzymes in colorectalcancer tissue and their differential activation by different bile-acids. Int J Cancer 61: 35-39
19. Serova M, Ghoul A, Benhadji KA, Cvitkovic E, Faivre S, Calvo F, Lokiec F, Raymond E (2006) Preclinical and Clinical Development of Novel Agents That Target the Protein Kinase C Family. Sem oncol 33: 466-478
20. Serova M, Ghoul A, Benhadji KA, Faivre S, Le Tourneau C, Cvitkovic E, Lokiec F, Lord J, Ogbourne SM, Calvo F, Raymond E (2008) Effects of PKC modulation by PEP005, a novel ingenol angelate, on MAPK and PI3K signaling in cancer cells. Mol Cancer Ther 7: 915-922
21. Suzuma K, Takahara N, Suzuma I, Isshiki K, Ueki K, Leitges M, Aiello LP, King GL (2002) Characterization of protein kinase Cβ isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization. Proc Natl Acad Sci 99: 721-726
22. Teicher BA, Menon K, Alvarez E, Galbreath E, Shih C, Faul MM (2001) Antiangiogenic and antitumor effects of a protein kinase C inhibitor in human HT-29 colon carcinoma and human CaKi1 renal cell carcinoma xenografts. Anticancer Res 21: 3175-3184
23. Verstovsek G, Byrd A, Frey MR, Petrelli NJ, Black JD (1998) Colonocyte differentiation is associated with increased expression and altered distribution of protein kinase C isozymes. Gastroenterology 115: 75-85
24. Zhang J, Anastasiadis PZ, Liu Y, Thompson EA, Fields AP (2004) Protein kinase C (PKC) II induces cell invasion through a Ras/Mek-, PKC /Rac1-dependent signaling pathway. J Biol Chem 279: 22118-22123