Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP-1 in human multiple myeloma cells

International Journal of Cancer

Volumn 127, Issue 2, 2010, Pages 282-292

  Pandey, Manoj K ^a   Sung, Bokyung ^a   Aggarwal, Bharat B ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Apoptosis; Betulinic acid; JAK1; JAK2; SHP 1; STAT3

Indexed keywords

BETULIC ACID; BORTEZOMIB; JANUS KINASE 1; JANUS KINASE 2; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PERVANADATE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE SHP 1; STAT3 PROTEIN; THALIDOMIDE; ANTINEOPLASTIC AGENT; BORONIC ACID DERIVATIVE; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 6; JAK1 PROTEIN, HUMAN; JAK2 PROTEIN, HUMAN; LUCIFERASE; PROTEINASE INHIBITOR; PTPN6 PROTEIN, HUMAN; PYRAZINE DERIVATIVE; STAT3 PROTEIN, HUMAN; TRITERPENE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; DRUG POTENTIATION; GENE SILENCING; HUMAN; HUMAN CELL; MULTIPLE MYELOMA; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; CELL PROLIFERATION; DRUG COMBINATION; DRUG EFFECT; ENZYME ACTIVATION; ENZYME IMMUNOASSAY; FLOW CYTOMETRY; GEL MOBILITY SHIFT ASSAY; GENETICS; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL CULTURE; WESTERN BLOTTING;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; BLOTTING, WESTERN; BORONIC ACIDS; CELL PROLIFERATION; DRUG THERAPY, COMBINATION; ELECTROPHORETIC MOBILITY SHIFT ASSAY; ENZYME ACTIVATION; FLOW CYTOMETRY; HUMANS; IMMUNOENZYME TECHNIQUES; IMMUNOSUPPRESSIVE AGENTS; INTERLEUKIN-6; JANUS KINASE 1; JANUS KINASE 2; LUCIFERASES; MULTIPLE MYELOMA; PROTEASE INHIBITORS; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 6; PYRAZINES; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES; STAT3 TRANSCRIPTION FACTOR; THALIDOMIDE; TRITERPENES; TUMOR CELLS, CULTURED;

EID: 77953690135     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.25059     Document Type: Article

References (34)

1. Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CW, Fong HH, Kinghorn AD, Brown DM, Wani MC, Wall ME, et al. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1995;1:1046-51.
2. Schmidt ML, Kuzmanoff KL, Ling-Indeck L, Pezzuto JM. Betulinic acid induces apoptosis in human neuroblastoma cell lines. Eur J Cancer 1997;33:2007-10. (Pubitemid 28123444)
3. Fulda S, Jeremias I, Steiner HH, Pietsch T, Debatin K-M. Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells. Int J Cancer 1999;82:435-41. (Pubitemid 29302986)
4. Rzeski W, Stepulak A, Szymanski M, Sifringer M, Kaczor J, Wejksza K, Zdzisinska B, Kandefer-Szerszen M. Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells. Naunyn Schmiedebergs Arch Pharmakol 2006;374:11-20.
5. Chintharlapalli S, Papineni S, Ramaiah SK, Safe S. Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors. Cancer Res 2007;67:2816-23. (Pubitemid 46548971)
6. Kashiwada Y, Hashimoto F, Cosentino LM, Chen CH, Garrett PE, Lee KH. Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents. J Med Chem1996;39:1016-17.
7. Darnell JE, Jr. Transcription factors as targets for cancer therapy. Nat Rev 2002;2:740-9.
8. Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, Sung B, Ichikawa H. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann NY Acad Sci 2006;1091:151-69. (Pubitemid 47092233)
9. Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood 1998;91:3-21. (Pubitemid 28018724)
10. Bharti AC, Shishodia S, Reuben JM, Weber D, Alexanian R, Raj-Vadhan S, Estrov Z, Talpaz M, Aggarwal BB. Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood 2004;103:3175-84.
11. Zhong Z, Wen Z, Darnell JE, Jr. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science (New York, NY) 1994;264:95-8. (Pubitemid 24144493)
12. Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J, Jove R. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science (New York, NY) 1995;269:81-3.
13. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988;332:83-5. (Pubitemid 18083553)
14. Ihle JN. STATs: signal transducers and activators of transcription. Cell 1996;84:331-4.
15. Han Y, Amin HM, Franko B, Frantz C, Shi X, Lai R. Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma. Blood 2006;108:2796-803.
16. Wu C, Sun M, Liu L, Zhou GW. The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene 2003;306:1-12. (Pubitemid 36351390)
17. Oka T, Ouchida M, Koyama M, Ogama Y, Takada S, Nakatani Y, Tanaka T, Yoshino T, Hayashi K, Ohara N, Kondo E, Takahashi K, et al. Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas. Cancer Res 2002;62:6390-4.
18. Yu H, Jove R. The STATs of cancer - new molecular targets come of age. Nat Rev 2004;4:97-105.
19. Matsushime H, Roussel MF, Ashmun RA, Sherr CJ. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell 1991;65:701-13.
20. Brierley MM, Fish EN. Stats: multifaceted regulators of transcription. J Interferon Cytokine Res 2005;25:733-44.
21. Bowman T, Garcia R, Turkson J, Jove R. STATs in oncogenesis. Oncogene 2000;19:2474-88.
22. Woetmann A, Nielsen M, Christensen ST, Brockdorff J, Kaltoft K, Engel AM, Skov S, Brender C, Geisler C, Svejgaard A, Rygaard J, Leick V, et al. Inhibition of protein phosphatase 2A induces serine/threonine phosphorylation, subcellular redistribution, and functional inhibition of STAT3. Proc Natl Acad Sci USA 1999;96:10620-5.
23. Kim H, Baumann H. Dual signaling role of the protein tyrosine phosphatase SHP-2 in regulating expression of acute-phase plasma proteins by interleukin-6 cytokine receptors in hepatic cells. Mol Cell Biol 1999;19:5326-38.
24. Takada Y, Aggarwal BB. Betulinic acid suppresses carcinogen-induced NF-κ B activation through inhibition of I κ B α kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9. J Immunol 2003;171:3278-86.
25. Digicaylioglu M, Lipton SA. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 2001;412:641-7.
26. Fulda S, Friesen C, Los M, Scaffidi C, Mier W, Benedict M, Nunez G, Krammer PH, Peter ME, Debetulinic acidtin KM. Betulinic acid triggers CD95 (APO-1/Fas)-and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer Res 1997;57:4956-64.
27. Ji ZN, Ye WC, Liu GG, Hsiao WL. 23-Hydroxybetulinic acid-mediated apoptosis is accompanied by decreases in bcl-2 expression and telomerase activity in HL-60 cells. Life Sci 2002;72:1-9. (Pubitemid 35284550)
28. Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R, Yu H. Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res 1999;59:5059-63. (Pubitemid 29503958)
29. Tu Y, Renner S, Xu F, Fleishman A, Taylor J, Weisz J, Vescio R, Rettig M, Berenson J, Krajewski S, Reed JC, Lichtenstein A. BCLX expression in multiple myeloma: possible indicator of chemoresistance. Cancer Res 1998;58:256-62. (Pubitemid 28047064)
30. Simonian PL, Grillot DA, Nunez G. Bcl-2 and Bcl-XL can differentially block chemotherapy-induced cell death. Blood 1997;90:1208-16. (Pubitemid 27314158)
31. Cavo M. Proteasome inhibitor bortezomib for the treatment of multiple myeloma. Leukemia 2006;20:1341-52. (Pubitemid 44084044)
32. Glasmacher A, Hahn C, Hoffmann F, Naumann R, Goldschmidt H, von Lilienfeld-Toal M, Orlopp K, Schmidt-Wolf I, Gorschluter M. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2006;132:584-93. (Pubitemid 43381591)
33. Liby K, Honda T, Williams CR, Risingsong R, Royce DB, Suh N, Dinkova-Kostova AT, Stephenson KK, Talalay P, Sundararajan C, Gribble GW, Sporn MB. Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities. Mol Cancer Ther 2007;6:2113-19. (Pubitemid 47052502)
34. Yu D, Morris-Natschke SL, Lee KH. New developments in natural products-betulinic acidsed anti-AIDS research. Med Res Rev 2007;27:108-32. (Pubitemid 44975188)