Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells

British Journal of Cancer

Volumn 111, Issue 7, 2014, Pages 1327-1337

  Siveen, K S ^a   Nguyen, A H ^a   Lee, J H ^b   Li, F ^a   Singh, S S ^a,c   Kumar, A P ^a,c,d,e   Low, G ^a,c   Jha, S ^a,c   Tergaonkar, V ^f   Ahn, K S ^b   Sethi, G ^a,c  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b Kyung Hee University   (South Korea)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^d CURTIN UNIVERSITY   (Australia)

^e UNIVERSITY OF NORTH TEXAS   (United States)

^f INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE 1; JANUS KINASE 2; LUPEOL; MESSENGER RNA; PERVANADATE; PROTEIN BAK; PROTEIN BAX; PROTEIN BID; PROTEIN TYROSINE PHOSPHATASE SHP 2; STAT3 PROTEIN; TYROSINE; VASCULOTROPIN; ANTINEOPLASTIC AGENT; APOPTOSIS REGULATORY PROTEIN; CXCL12 PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR; JAK1 PROTEIN, HUMAN; JAK2 PROTEIN, HUMAN; PENTACYCLIC TRITERPENE; STAT3 PROTEIN, HUMAN; STROMAL CELL DERIVED FACTOR 1; VASCULOTROPIN A; VEGFA PROTEIN, HUMAN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CARCINOMA CELL; CELL CYCLE G1 PHASE; CELL MIGRATION; CELL PROLIFERATION; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DNA BINDING; DOSE TIME EFFECT RELATION; DOWN REGULATION; DRUG STRUCTURE; ENZYME INHIBITION; GENE EXPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; ONCOGENE SRC; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REPORTER GENE; SIGNAL TRANSDUCTION; TREATMENT DURATION; CELL MOTION; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; HEPG2 CELL LINE; LIVER TUMOR; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN BINDING; PROTEIN PROCESSING; TRANSCRIPTION INITIATION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CARCINOMA, HEPATOCELLULAR; CELL MOVEMENT; CELL PROLIFERATION; CHEMOKINE CXCL12; EPIDERMAL GROWTH FACTOR; GENE EXPRESSION REGULATION, NEOPLASTIC; HEP G2 CELLS; HUMANS; JANUS KINASE 1; JANUS KINASE 2; LIVER NEOPLASMS; PENTACYCLIC TRITERPENES; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TRANSCRIPTIONAL ACTIVATION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84909993580     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2014.422     Document Type: Article

References (45)

1. Baffy G, Brunt EM, Caldwell SH (2012) Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace. J Hepatol 56(6): 1384-1391.
2. Bhutani M, Pathak AK, Nair AS, Kunnumakkara AB, Guha S, Sethi G, Aggarwal BB (2007) Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation. Clin Cancer Res 13(10): 3024-3032.
3. Bromberg J, Wang TC (2009) Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 15(2): 79-80.
4. Burke WM, Jin X, Lin HJ, Huang M, Liu R, Reynolds RK, Lin J (2001) Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells. Oncogene 20(55): 7925-7934.
5. Cervello M, McCubrey JA, Cusimano A, Lampiasi N, Azzolina A, Montalto G (2012) Targeted therapy for hepatocellular carcinoma: novel agents on the horizon. Oncotarget 3(3): 236-260.
6. Chen RH, Chang MC, Su YH, Tsai YT, Kuo ML (1999) Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways. J Biol Chem 274(33): 23013-23019.
7. Cormier JN, Thomas KT, Chari RS, Pinson CW (2006) Management of hepatocellular carcinoma. J Gastrointest Surg 10(5): 761-780.
8. Dechow TN, Pedranzini L, Leitch A, Leslie K, Gerald WL, Linkov I, Bromberg JF (2004) Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C. Proc Natl Acad Sci USA 101(29): 10602-10607.
9. Dey A, Wong E, Kua N, Teo HL, Tergaonkar V, Lane D (2008) Hexamethylene bisacetamide (HMBA) simultaneously targets AKT and MAPK pathway and represses NF-kB activity. Cell Cycle 7(23): 3759-3767.
10. Fuke H, Shiraki K, Sugimoto K, Tanaka J, Beppu T, Yoneda K, Yamamoto N, Ito K, Masuya M, Takei Y (2007) Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 363(3): 738-744.
11. Garcia R, Bowman TL, Guillian N, Hua Y, Minton S, Muro-Cacho CA, Cox CE, Falcone R, Fairclough R, Parsons S (2001) Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20(20): 2499-2513.
12. Ghosh A, Saginc G, Leow SC, Khattar E, Shin EM, Yan TD, Wong M, Zhang Z, Li G, Sung WK (2012) Telomerase directly regulates NF-kB-dependent transcription. Nat Cell Biol 14(12): 1270-1281.
13. Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, Nam S, Eweis I, Diaz N, Sullivan D, Yoder S, Enkemann S, Eschrich S, Lee JH, Beam CA, Cheng J, Minton S, Muro-Cacho CA, Jove R (2006) Persistent activation of Stat3 signaling induces Survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res 12(1): 11-19.
14. Grivennikov SI, Karin M (2010) Dangerous liaisons: STAT3 and NF-kB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 21(1): 11-19.
15. Ihle JN (1996) STATs: signal transducers and activators of transcription. Cell 84(3): 331-334.
16. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2): 69-90.
17. Johnston PA, Grandis JR (2011) STAT3 signaling: anticancer strategies and challenges. Mol Interv 11(1): 18-26.
18. Kannaiyan R, Hay HS, Rajendran P, Li F, Shanmugam MK, Vali S, Abbasi T, Kapoor S, Sharma A, Kumar AP (2011) Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-kB and STAT3 regulated gene products in multiple myeloma cells. Br J Pharmacol 164(5): 1506-1521.
19. Kim C, Cho SK, Kapoor S, Kumar A, Vali S, Abbasi T, Kim SH, Sethi G, Ahn KS (2013) b-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP1 protein tyrosine phosphatase. Mol Carcinog; e-pub ahead of print 13 June 2013; doi:10.1002/mc.22035.
20. Lee H, Herrmann A, Deng JH, Kujawski M, Niu G, Li Z, Forman S, Jove R, Pardoll DM, Yu H (2009) Persistently activated Stat3 maintains constitutive NF-kB activity in tumors. Cancer Cell 15(4): 283-293.
21. Lee TK, Poon RTP, Wo JY, Ma S, Guan XY, Myers JN, Altevogt P, Yuen APW (2007) Lupeol suppresses cisplatin-induced nuclear factor-kB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse model. Cancer Res 67(18): 8800-8809.
22. Lee TKW, Castilho A, Cheung VCH, Tang KH, Ma S, Ng IOL (2011a) CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 9(1): 50-63.
23. Lee TKW, Castilho A, Cheung VCH, Tang KH, Ma S, Ng IOL (2011b) Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation. Hepatology 53(1): 160-170.
24. Lepiller Q, Abbas W, Kumar A, Tripathy MK, Herbein G (2013) HCMV activates the IL-6-JAK-STAT3 axis in HepG2 cells and primary human hepatocytes. PLoS One 8(3): e59591.
25. Li F, Shanmugam MK, Chen L, Chatterjee S, Basha J, Kumar AP, Kundu TK, Sethi G (2013) Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma. Cancer Prev Res (Phila) 6(8): 843-854.
26. Li WC, Ye SL, Sun RX, Liu YK, Tang ZY, Kim Y, Karras JG, Zhang H (2006) Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res 12(23): 7140-7148.
27. Newman DJ (2008) Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J Med Chem 51(9): 2589-2599.
28. Page BD, Ball DP, Gunning PT (2011) Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin Ther Pat 211: 65-83.
29. Prasad S, Madan E, Nigam N, Roy P, George J, Shukla Y (2009) Induction of apoptosis by lupeol in human epidermoid carcinoma A431 cells through regulation of mitochondrial, Akt/PKB and NF-kappaB signaling pathways. Cancer Biol Ther 8(17): 1632-1639.
30. Rajendran P, Li F, Manu KA, Shanmugam MK, Loo SY, Kumar AP, Sethi G (2011) g-Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: potential role as an antiproliferative, pro-apoptotic and chemosensitizing agent. Br J Pharmacol 163(2): 283-298.
31. Rajendran P, Li F, Shanmugam MK, Kannaiyan R, Goh JN, Wong KF, Wang W, Khin E, Tergaonkar V, Kumar AP (2012) Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo. Cancer Prev Res (Phila) 5(4): 631-643.
32. Raskopf E, Vogt A, Sauerbruch T, Schmitz V (2008) siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo. J Hepatol 49(6): 977-984.
33. Shanmugam MK, Rajendran P, Li F, Nema T, Vali S, Abbasi T, Kapoor S, Sharma A, Kumar AP, Ho PC (2011) Ursolic acid inhibits multiple cell survival pathways leading to suppression of growth of prostate cancer xenograft in nude mice. J Mol Med 89(7): 713-727.
34. Shuai K, Liu B (2003) Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3(11): 900-911.
35. Siddique HR, Mishra SK, Karnes RJ, Saleem M (2011) Lupeol, a novel androgen receptor inhibitor: implications in prostate cancer therapy. Clin Cancer Res 17(16): 5379-5391.
36. Siddique HR, Saleem M (2011) Beneficial health effects of lupeol triterpene: a review of preclinical studies. Life Sci 88(7-8): 285-293.
37. Subramaniam A, Shanmugam MK, Perumal E, Li F, Nachiyappan A, Dai X, Swamy SN, Ahn KS, Kumar AP, Tan BKH, Hui KM, Sethi G (2013) Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta 1835(1): 46-60.
38. Tarapore RS, Siddiqui IA, Saleem M, Adhami VM, Spiegelman VS, Mukhtar H (2010) Specific targeting of Wnt/b-catenin signaling in human melanoma cells by a dietary triterpene lupeol. Carcinogenesis 31(10): 1844-1853.
39. Wang H, Lafdil F, Kong X, Gao B (2011) Signal transducer and activator of transcription 3 in liver diseases: a novel therapeutic target. Int J Biol Sci 7(5): 536-550.
40. Wormald S, Hilton DJ (2004) Inhibitors of cytokine signal transduction. J Biol Chem 279(2): 821-824.
41. Xu D, Qu C-K (2008) Protein tyrosine phosphatases in the JAK/STAT pathway. Front Biosci 13: 4925-4932.
42. Yang F, Brown C, Buettner R, Hedvat M, Starr R, Scuto A, Schroeder A, Jensen M, Jove R (2010) Sorafenib induces growth arrest and apoptosis of human glioblastoma cells through the dephosphorylation of signal transducers and activators of transcription 3. Mol Cancer Ther 9(4): 953-962.
43. Yu C-L, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J, Jove R (1995) Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269(5220): 81-83.
44. Yue P, Turkson J (2009) Targeting STAT3 in cancer: how successful are we? Expert Opin Invest Drugs 18(1): 45-56.
45. Zhang Q, Raghunath PN, Xue L, Majewski M, Carpentieri DF, Odum N, Morris S, Skorski T, Wasik MA (2002) Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma. J Immunol 168(1): 466-474.