Apigenin blocks IKKa activation and suppresses prostate cancer progression

Oncotarget

Volumn 6, Issue 31, 2015, Pages 31216-31232

  Shukla, Sanjeev ^a,b   Kanwal, Rajnee ^a,b   Shankar, Eswar ^a,b   Datt, Manish ^c   Chance, Mark R ^c   Fu, Pingfu ^c   MacLennan, Gregory T ^a   Gupta, Sanjay ^a,b,d  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d LOUIS STOKES CLEVELAND VA MEDICAL CENTER   (United States)

Author keywords

Apigenin; Cell cycle; NF B signaling; Prostate cancer; Therapeutic target

Indexed keywords

6 CHLORO 8 NICOTINAMIDO BETA CARBOLINE; APIGENIN; CASPASE 3; CYCLINE; I KAPPA B KINASE ALPHA; I KAPPA B KINASE BETA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; TRANSCRIPTION FACTOR RELA; I KAPPA B KINASE;

22RV1 CELL LINE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; BINDING AFFINITY; CANCER GROWTH; CANCER INHIBITION; CELL CYCLE ARREST; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG PROTEIN BINDING; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME LINKED IMMUNOSORBENT ASSAY; EX VIVO STUDY; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; INHIBITION KINETICS; MALE; MIGRATION INHIBITION; MOLECULAR DOCKING; MOLECULAR MODEL; MOUSE; NONHUMAN; PC 3 CELL LINE; PROSTATE CANCER; PROSTATE CANCER CELL LINE; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN INDUCTION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; TREATMENT DURATION; TUMOR INVASION; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CYCLE; CELL MOTION; CELL PROLIFERATION; DISEASE COURSE; DRUG EFFECTS; DRUG SCREENING; ENZYME IMMUNOASSAY; METABOLISM; PATHOLOGY; PHOSPHORYLATION; PROSTATIC NEOPLASMS; TUMOR CELL CULTURE; WESTERN BLOTTING; WOUND HEALING;

ANIMALS; APIGENIN; APOPTOSIS; BLOTTING, WESTERN; CELL CYCLE; CELL MOVEMENT; CELL PROLIFERATION; DISEASE PROGRESSION; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; I-KAPPA B KINASE; IMMUNOENZYME TECHNIQUES; MALE; MICE; PHOSPHORYLATION; PROSTATIC NEOPLASMS; SIGNAL TRANSDUCTION; TUMOR CELLS, CULTURED; WOUND HEALING; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84945576789     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5157     Document Type: Article

References (55)

1. Häcker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006; 2006; (357):re13.
2. Huang WC, Hung MC. Beyond NF-κB activation: nuclear functions of IκB kinase α. J Biomed Sci. 2013; 20:3.
3. Gamble C, McIntosh K, Scott R, Ho KH, Plevin R, Paul A. Inhibitory kappa B Kinases as targets for pharmacological regulation. Br J Pharmacol. 2012; 165:802-819.
4. Suzuki J, Ogawa M, Muto S, Itai A, Isobe M, Hirata Y, Nagai R. Novel IkB kinase inhibitors for treatment of nuclear factor-kB-related diseases. Expert Opin Investig Drugs. 2011; 20:395-405.
5. Napetschnig J, Wu H. Molecular basis of NF-κB signaling. Annu Rev Biophys. 2013; 42:443-468.
6. Liu F, Xia Y, Parker AS, Verma IM. IKK biology. Immunol Rev. 2012; 246:239-253.
7. Solt LA, May MJ. The IkappaB kinase complex: master regulator of NF-kappaB signaling. Immunol Res. 2008; 42:3-18.
8. Bassères DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 2006; 25:6817-6830.
9. Clément JF, Meloche S, Servant MJ. The IKK-related kinases: from innate immunity to oncogenesis. Cell Res. 2008; 18:889-899.
10. Nguyen DP, Li J, Yadav SS, Tewari AK. Recent insights into NF-κB signaling pathways and the link between inflammation and prostate cancer. BJU Int. 2014; 114:168-76.
11. Gasparian AV, Yao YJ, Kowalczyk D, Lyakh LA, Karseladze A, Slaga TJ, Budunova IV. The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells. J Cell Sci. 2002; 115:141-151.
12. Shukla S, Maclennan GT, Marengo SR, Resnick MI, Gupta S. Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model. Prostate. 2005; 64:224-239.
13. Suh J, Payvandi F, Edelstein LC, Amenta PS, Zong WX, Gélinas C, Rabson AB. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 2002; 52:183-200.
14. Yemelyanov A, Gasparian A, Lindholm P, Dang L, Pierce JW, Kisseljov F, Karseladze A, Budunova I. Effects of IKK inhibitor PS1145 on NF-kappaB function, proliferation, apoptosis and invasion activity in prostate carcinoma cells. Oncogene. 2006; 25:387-398.
15. Fahy BN, Schlieman MG, Mortenson MM, Virudachalam S, Bold RJ. Targeting BCL-2 overexpression in various human malignancies through NF-kappaB inhibition by the proteasome inhibitor bortezomib. Cancer Chemother Pharmacol. 2005; 56:46-54.
16. Jain G, Voogdt C, Tobias A, Spindler KD, Möller P, Cronauer MV, Marienfeld RB. IκB kinases modulate the activity of the androgen receptor in prostate carcinoma cell lines. Neoplasia. 2012; 14:178-189.
17. Papandreou CN, Daliani DD, Nix D, Yang H, Madden T, Wang X, Pien CS, Millikan RE, Tu SM, Pagliaro L, Kim J, Adams J, Elliott P, Esseltine D, Petrusich A, Dieringer P, Perez C, Logothetis CJ. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol. 2004; 22:2108-2121.
18. Kraft AS, Garrett-Mayer E, Wahlquist AE, Golshayan A, Chen CS, Butler W, Bearden J, Lilly M. Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade. Cancer Biol Ther. 2011; 12:119-124.
19. Manna S, Singha B, Phyo SA, Gatla HR, Chang TP, Sanacora S, Ramaswami S, Vancurova I. Proteasome inhibition by bortezomib increases IL-8 expression in androgen-independent prostate cancer cells: the role of IKKa. J Immunol. 2013; 191:2837-2846.
20. Mahato R, Qin B, Cheng K. Blocking IKKa expression inhibits prostate cancer invasiveness. Pharm Res. 2011; 28:1357-1369.
21. Luo JL, Tan W, Ricono JM, Korchynskyi O, Zhang M, Gonias SL, Cheresh DA, Karin M. Nuclear cytokineactivated IKKalpha controls prostate cancer metastasis by repressing Maspin. Nature. 2007; 446:690-694.
22. Xu C, Shen G, Chen C, Gélinas C, Kong AN. Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene. 2005; 24:4486-4495.
23. Rabi T, Shukla S, Gupta S. Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells. Mol Carcinog. 2008; 47:964-973.
24. Syrovets T, Gschwend JE, Büchele B, Laumonnier Y, Zugmaier W, Genze F, Simmet T. Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. J Biol Chem. 2005; 280:6170-6180.
25. Anand P, Sung B, Kunnumakkara AB, Rajasekharan KN, Aggarwal BB. Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors. Biochem Pharmacol. 2011; 82:1901-1909.
26. Weng CJ, Yen GC. Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev. 2012; 31:323-351.
27. Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010; 27:962-978.
28. Gupta S, Afaq F, Mukhtar H. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene. 2002; 21:3727-3738.
29. Way TD, Kao MC, Lin JK. Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem. 2004; 279:4479-4489.
30. Turktekin M, Konac E, Onen HI, Alp E, Yilmaz A, Menevse S. Evaluation of the effects of the flavonoid apigenin on apoptotic pathway gene expression on the colon cancer cell line (HT29). J Med Food. 2011; 14:1107-1117.
31. Wu DG, Yu P, Li JW, Jiang P, Sun J, Wang HZ, Zhang LD, Wen MB, Bie P. Apigenin potentiates the growth inhibitory effects by IKK-β-mediated NF-κB activation in pancreatic cancer cells. Toxicol Lett. 2014; 224:157-164.
32. Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, Guttridge DC, Grotewold E, Doseff AI. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol. 2007; 179:7121-7127.
33. Shukla S, Gupta S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: correlation with down-regulation of NF-kappaB-responsive genes. Clin Cancer Res. 2004; 10:3169-178.
34. Shukla S, MacLennan GT, Flask CA, Fu P, Mishra A, Resnick MI, Gupta S. Blockade of beta-catenin signaling by plant flavonoid apigenin suppresses prostate carcinogenesis in TRAMP mice. Cancer Res. 2007; 67:6925-6935.
35. Llona-Minguez S, Baiget J, Mackay SP. Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases. Pharm Pat Anal. 2013; 2:481-498.
36. Suzuki J, Ogawa M, Muto S, Itai A, Isobe M, Hirata Y, Nagai R. Novel IkB kinase inhibitors for treatment of nuclear factor-kB-related diseases. Expert Opin Investig Drugs. 2011; 20:395-405.
37. Lee DF, Hung MC. Advances in targeting IKK and IKKrelated kinases for cancer therapy. Clin Cancer Res. 2008; 14:5656-5662.
38. Ruocco MG, Karin M. IKK{beta} as a target for treatment of inflammation induced bone loss. Ann Rheum Dis. 2005; 64:iv81-5.
39. Schmid JA, Birbach A. IkappaB kinase beta (IKKbeta/IKK2/IKBKB)-a key molecule in signaling to the transcription factor NF-kappaB. Cytokine Growth Factor Rev. 2008; 19:157-165.
40. Kwak YT, Radaideh SM, Ding L, Li R, Frenkel E, Story MD, Girard L, Minna J, Verma UN. Cells lacking IKKa show nuclear cyclin D1 overexpression and a neoplastic phenotype: role of IKKa as a tumor suppressor. Mol Cancer Res. 2011; 9:341-349.
41. Deng L, Li Y, Ai P, Xie Y, Zhu H, Chen N. Increase in IkappaB kinase alpha expression suppresses the tumor progression and improves the prognosis for nasopharyngeal carcinoma. Mol Carcinog. 2015; 54:156-165.
42. Cao Y, Luo JL, Karin M. IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells. Proc Natl Acad Sci U S A. 2007; 104:15852-15857.
43. Ammirante M, Kuraishy AI, Shalapour S, Strasner A, Ramirez-Sanchez C, Zhang W, Shabaik A, Karin M. An IKKa-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence. Genes Dev. 2013; 27:1435-1440.
44. Yamamoto Y, Yin MJ, Gaynor RB. IkappaB kinase alpha (IKKalpha) regulation of IKKbeta kinase activity. Mol Cell Biol. 2000; 20:3655-3666.
45. Gupta SC, Kim JH, Prasad S, Aggarwal BB. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev. 2010; 29:405-434.
46. Shukla S, Gupta S. Apigenin suppresses insulin-like growth factor I receptor signaling in human prostate cancer: an in vitro and in vivo study. Mol Carcinog. 2009; 48:243-252.
47. Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem. 1997; :28-29. 39-48.
48. Tong X, Pelling JC. Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer Agents Med Chem. 2013; 13:971-978.
49. Pham H, Chen M, Takahashi H, King J, Reber HA, Hines OJ, Pandol S, Eibl G. Apigenin inhibits NNKinduced focal adhesion kinase activation in pancreatic cancer cells. Pancreas. 2012; 41:1306-1315.
50. Mirzoeva S, Franzen CA, Pelling JC. Apigenin inhibits TGF-β-induced VEGF expression in human prostate carcinoma cells via a Smad2/3-and Src-dependent mechanism. Mol Carcinog. 2014; 53:598-609.
51. Chuang KA, Lieu CH, Tsai WJ, Huang WH, Lee AR, Kuo YC. 3-methoxyapigenin modulates β-catenin stability and inhibits Wnt/β-catenin signaling in Jurkat leukemic cells. Life Sci. 2013; 92:677-686.
52. Singh V, Sharma V, Verma V, Pandey D, Yadav SK, Maikhuri JP, Gupta G. Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-b from degradation and induce apoptosis in prostate cancer cells. Eur J Nutr. 2014 Nov 19. [Epub ahead of print] PubMed PMID: 25408199.
53. Sharma H, Kanwal R, Bhaskaran N, Gupta S. Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells. PLoS One. 2014; 9:e91588.
54. Arango D, Morohashi K, Yilmaz A, Kuramochi K, Parihar A, Brahimaj B, Grotewold E, Doseff AI. Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets. Proc Natl Acad Sci U S A. 2013; 110:E2153-2162.
55. Deb G, Thakur VS, Limaye AM, Gupta S. Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells. Mol Carcinog. 2015; 54:485-499.