The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity

Molecular Cancer

Volumn 9, Issue , 2010, Pages

  Bill, Matthew A ^a   Fuchs, James R ^b   Li, Chenglong ^b   Yui, Jennifer ^a   Bakan, Courtney ^a   Benson Jr, Don M ^a   Schwartz, Eric B ^b   Abdelhamid, Dalia ^b   Lin, Jiayuh ^c   Hoyt, Dale G ^b   Fossey, Stacey L ^b   Young, Gregory S ^b   Carson III, William E ^a   Li, Pui Kai ^b   Lesinski, Gregory B ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE; COMPOUND FLLL32; CURCUMIN; CYTOKINE; DIMETHYL SULFOXIDE; GAMMA INTERFERON; GRANZYME B; INTERLEUKIN 2; INTERLEUKIN 6; JSI 124; LIPOCORTIN 5; PROPIDIUM IODIDE; PROTEIN INHIBITOR; STAT PROTEIN; STAT1 PROTEIN; STAT3 PROTEIN; STATTIC; TYROSINE; UNCLASSIFIED DRUG; WP 1066; DRUG DERIVATIVE; FLLL 32;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL ISOLATION; CELL VIABILITY; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; FLOW CYTOMETRY; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOCOMPETENT CELL; MELANOMA; MELANOMA CELL; MITOCHONDRIAL MEMBRANE POTENTIAL; NATURAL KILLER CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEIN PHOSPHORYLATION; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; DRUG ANTAGONISM; DRUG EFFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOLOGY; METABOLISM; PATHOLOGY; PHYSIOLOGY; POLYMERASE CHAIN REACTION; TUMOR CELL LINE; WESTERN BLOTTING;

APOPTOSIS; BLOTTING, WESTERN; CELL LINE, TUMOR; CURCUMIN; CYTOKINES; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENE EXPRESSION; HUMANS; MELANOMA; POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 77954613878     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-9-165     Document Type: Article

References (43)

1. Kortylewski M, Jove R, Yu H. Targeting STAT3 affects melanoma on multiple fronts. Cancer Metastasis Rev 2005, 24:315-327. 10.1007/s10555-005-1580-1, 15986140.
2. Niu G, Bowman T, Huang M, Shivers S, Reintgen D, Daud A, Chang A, Kraker A, Jove R, Yu H. Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene 2002, 21:7001-7010. 10.1038/sj.onc.1205859, 12370822.
3. Xie TX, Huang FJ, Aldape KD, Kang SH, Liu M, Gershenwald JE, Xie K, Sawaya R, Huang S. Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res 2006, 66:3188-3196. 10.1158/0008-5472.CAN-05-2674, 16540670.
4. Sellers LA, Feniuk W, Humphrey PP, Lauder H. Activated G protein-coupled receptor induces tyrosine phosphorylation of STAT3 and agonist-selective serine phosphorylation via sustained stimulation of mitogen-activated protein kinase. Resultant effects on cell proliferation. J Biol Chem 1999, 274:16423-16430. 10.1074/jbc.274.23.16423, 10347203.
5. Zhang Y, Turkson J, Carter-Su C, Smithgall T, Levitzki A, Kraker A, Krolewski JJ, Medveczky P, Jove R. Activation of Stat3 in v-Src-transformed fibroblasts requires cooperation of Jak1 kinase activity. J Biol Chem 2000, 275:24935-24944. 10.1074/jbc.M002383200, 10823829.
6. Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene 2000, 19:2607-2611. 10.1038/sj.onc.1203478, 10851059.
7. Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 1997, 94:3801-3804. 10.1073/pnas.94.8.3801, 20521, 9108058.
8. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol 2008, 75:787-809. 10.1016/j.bcp.2007.08.016, 17900536.
9. Bush JA, Cheung KJ, Li G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 2001, 271:305-314. 10.1006/excr.2001.5381, 11716543.
10. Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer 2005, 104:879-890. 10.1002/cncr.21216, 16007726.
11. Zheng M, Ekmekcioglu S, Walch ET, Tang CH, Grimm EA. Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res 2004, 14:165-171. 10.1097/01.cmr.0000129374.76399.19, 15179184.
12. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001, 21:2895-2900.
13. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998, 64:353-356. 10.1055/s-2006-957450, 9619120.
14. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol 2008, 76:1590-1611. 10.1016/j.bcp.2008.08.008, 18775680.
15. Bill MA, Bakan C, Benson DM, Fuchs J, Young G, Lesinski GB. Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines. Mol Cancer Ther 2009, 8:2726-2735. 10.1158/1535-7163.MCT-09-0377, 19723881.
16. Lin L, Hutzen B, Zuo M, Ball S, Deangelis S, Foust E, Pandit B, Ihnat MA, Shenoy SS, Kulp S, Li PK, Li C, Fuchs J, Lin J. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res 70:2445-2454. 10.1158/0008-5472.CAN-09-2468, 20215512.
17. Lesinski GB, Trefry J, Brasdovich M, Kondadasula SV, Sackey K, Zimmerer JM, Chaudhury AR, Yu L, Zhang X, Crespin TR, Walker MJ, Carson WE. Melanoma cells exhibit variable signal transducer and activator of transcription 1 phosphorylation and a reduced response to IFN-alpha compared with immune effector cells. Clin Cancer Res 2007, 13:5010-5019. 3, 10.1158/1078-0432.CCR-06-3092, 17785551.
18. Satyamoorthy K, DeJesus E, Linnenbach AJ, Kraj B, Kornreich DL, Rendle S, Elder DE, Herlyn M. Melanoma cell lines from different stages of progression and their biological and molecular analyses. Melanoma Res 1997, 7(Suppl 2):S35-42.
19. Priebe W, Donato N, Talpaz M, Szymanshi S, Fokt I, Levitki A. Preparation of benzyl cyanocinnamides and related compounds for treatment of cell proliferative diseases. pp. PCT Int. Appl.; 2005: PCT Int. Appl.
20. Park BS, Kim JG, Kim MR, Lee SE, Takeoka GR, Oh KB, Kim JH. Curcuma longa L. constituents inhibit sortase A and Staphylococcus aureus cell adhesion to fibronectin. J Agric Food Chem 2005, 53:9005-9009. 10.1021/jf051765z, 16277395.
21. Venkateswarlu S, Ramachandra MS, Subbaraju GV. Synthesis and biological evaluation of polyhydroxycurcuminoids. Bioorg Med Chem 2005, 13:6374-6380. 10.1016/j.bmc.2005.06.050, 16112582.
22. Lesinski GB, Kondadasula SV, Crespin T, Shen L, Kendra K, Walker MJ, Carson WE. Multiparametric flow cytometric analysis of inter-patient variation in STAT1 phosphorylation following interferon alfa immunotherapy. J Natl Cancer Inst 2004, 96:1331-1342. 10.1093/jnci/djh252, 15339971.
23. Lesinski GB, Raig T, Guenterberg K, Brown L, Go M, Shah N, Lewis A, Quimper M, Hade E, Young G, Chaudhury AR, Ladner KJ, Guttridge DC, Bouchard P, Carson WE. IFN-alpha and bortezomib overcome Bcl-2 and Mcl-1 overexpression in melanoma cells by stimulating the extrinsic pathway of apopotsis. Cancer Res 2008, 68:8351-8360. 3, 10.1158/0008-5472.CAN-08-0426, 2631434, 18922907.
24. Li Y, Upadhyay S, Bhuiyan M, Sarkar FH. Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein. Oncogene 1999, 18:3166-3172. 10.1038/sj.onc.1202650, 10340389.
25. Ramsauer K, Sadzak I, Porras A, Pilz A, Nebreda AR, Decker T, Kovarik P. p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation. Proc Natl Acad Sci USA 2002, 99:12859-12864. 10.1073/pnas.192264999, 130550, 12232043.
26. Zimmerer JM, Lesinski GB, Kondadasula SV, Karpa VI, Lehman A, Raychaudhury A, Becknell B, Carson WE. IFN-alpha-induced signal transduction, gene expression, and antitumor activity of immune effector cells are negatively regulated by suppressor of cytokine signaling proteins. J Immunol 2007, 178:4832-4845. 3.
27. Shafer-Weaver KA, Sayers T, Kuhns DB, Strobl SL, Burkett MW, Baseler M, Malyguine A. Evaluating the cytotoxicity of innate immune effector cells using the GrB ELISPOT assay. J Transl Med 2004, 2:31. 10.1186/1479-5876-2-31, 522821, 15380049.
28. Hill A. The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 1910, 40:iv-vii.
29. Sengupta TK, Talbot ES, Scherle PA, Ivashkiv LB. Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases. Proc Natl Acad Sci USA 1998, 95:11107-11112. 10.1073/pnas.95.19.11107, 21603, 9736697.
30. Bromberg J. Stat proteins and oncogenesis. J Clin Invest 2002, 109:1139-1142. 150969, 11994401.
31. Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE. Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci USA 1996, 93:7673-7678. 10.1073/pnas.93.15.7673, 38805, 8755534.
32. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE. Stat3 as an oncogene. Cell 1999, 98:295-303. 10.1016/S0092-8674(00)81959-5, 10458605.
33. Fletcher S, Turkson J, Gunning PT. Molecular approaches towards the inhibition of the signal transducer and activator of transcription 3 (Stat3) protein. ChemMedChem 2008, 3:1159-1168. 10.1002/cmdc.200800123, 2603136, 18683176.
34. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol 2006, 6:836-848. 10.1038/nri1961, 17063185.
35. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 1982, 155:1823-1841. 10.1084/jem.155.6.1823, 2186695, 6176669.
36. Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res 1981, 41:4420-4425.
37. Lin L, Hutzen B, Li PK, Ball S, Zuo M, DeAngelis S, Foust E, Sobo M, Friedman L, Bhasin D, Cen L, Li C, Lin J. A novel small molecule, LLL12, inhibits STAT3 phosphorylation and activities and exhibits potent growth-suppressive activity in human cancer cells. Neoplasia 12:39-50. 2805882, 20072652.
38. Turkson J, Zhang S, Palmer J, Kay H, Stanko J, Mora LB, Sebti S, Yu H, Jove R. Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity. Mol Cancer Ther 2004, 3:1533-1542.
39. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007, 7:41-51. 10.1038/nri1995, 17186030.
40. Wang W, Edington HD, Rao UN, Jukic DM, Land SR, Ferrone S, Kirkwood JM. Modulation of signal transducers and activators of transcription 1 and 3 signaling in melanoma by high-dose IFNalpha2b. Clin Cancer Res 2007, 13:1523-1531. 10.1158/1078-0432.CCR-06-1387, 17332298.
41. Tartour E, Dorval T, Mosseri V, Deneux L, Mathiot C, Brailly H, Montero F, Joyeux I, Pouillart P, Fridman WH. Serum interleukin 6 and C-reactive protein levels correlate with resistance to IL-2 therapy and poor survival in melanoma patients. Br J Cancer 1994, 69:911-913. 1968905, 8180022.
42. Kong LY, Gelbard A, Wei J, Reina-Ortiz C, Wang Y, Yang EC, Hailemichael Y, Fokt I, Jayakumar A, Qiao W, Fuller GN, Overwijk WW, Priebe W, Heimberger AB. Inhibition of p-STAT3 enhances IFN-alpha efficacy against metastatic melanoma in a murine model. Clin Cancer Res 16:2550-2561. 10.1158/1078-0432.CCR-10-0279, 20388845.
43. Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, Lee H, Scuto A, Liu Y, Yang C, Deng J, Soifer HS, Raubitschek A, Forman S, Rossi JJ, Pardoll DM, Jove R, Yu H. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol 2009, 27:925-932. 10.1038/nbt.1564, 2846721, 19749770.