A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways

Toxicology and Applied Pharmacology

Volumn 272, Issue 3, 2013, Pages 852-862

  Gan, Fei Fei ^a   Ling, Hui ^a,c   Ang, Xiaohui ^a   Reddy, Shridhivya A ^a   Lee, Stephanie S H ^a   Yang, Hong ^a   Tan, Sock Hoon ^a   Hayes, John D ^b   Chui, Wai Keung ^a   Chew, Eng Hui ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b UNIVERSITY OF DUNDEE   (United Kingdom)

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

Author keywords

Chemoprevention; Ginger; Michael acceptors; NF B; Nrf2 Keap1; Shogaols

Indexed keywords

3 PHENYL 3 SHOGAOL; 6 SHOGAOL; CYCLOOXYGENASE 2; CYSTEINE; DESHYDROXY 3 PHENYL 3 SHOGAOL; GELATINASE B; HEME OXYGENASE 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; KELCH LIKE ECH ASSOCIATED PROTEIN 1; NITRIC OXIDE; OXIDOREDUCTASE; PHORBOL 13 ACETATE 12 MYRISTATE; PROSTAGLANDIN E2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SHOGAOL; TRANSCRIPTION FACTOR NRF2; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT RESPONSIVE ELEMENT; ARTICLE; BIOLOGICAL ACTIVITY; BREAST CARCINOMA; CANCER INHIBITION; CARCINOMA CELL; CELL PROTECTION; CELL STRAIN MCF 7; CELL STRESS; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG EFFECT; EMBRYO; ENZYME ACTIVATION; ENZYME REPRESSION; ENZYME SUBSTRATE; FEMALE; HUMAN; HUMAN CELL; INFLAMMATION; INTRACELLULAR SIGNALING; MACROPHAGE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN EXPRESSION; TUMOR INVASION;

ANTIOXIDANT RESPONSE ELEMENT; ARE; CHEMOPREVENTION; COX-2; CYCLOOXYGENASE-2; ECM; EXTRACELLULAR MATRIX; GINGER; HEME OXYGENASE-1; HO-1; IΚB KINASE; IΚBΑ; IKK; INDUCIBLE NITRIC OXIDE SYNTHASE; INHIBITOR OF KAPPABΑ; INOS; KEAP1; KELCH-LIKE ECH-ASSOCIATED PROTEIN 1; MATRIX METALLOPROTEINASE; MICHAEL ACCEPTORS; MMP; NAD(P)H QUINONE OXIDOREDUCTASE-1; NF-ΚB; NF-E2 P45-RELATED FACTOR 2; NQO1; NRF2; NRF2-KEAP1; NUCLEAR FACTOR-ΚB; PGE(2); PHORBOL 12-MYRISTATE 13-ACETATE; PMA; PROSTANGLANDIN-E(2); SHOGAOLS;

ANIMALS; CATECHOLS; CYTOPROTECTION; DOWN-REGULATION; HEK293 CELLS; HUMANS; INFLAMMATION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MCF-7 CELLS; MICE; NEOPLASM INVASIVENESS; NF-E2-RELATED FACTOR 2; NF-KAPPA B; PLANT EXTRACTS; SIGNAL TRANSDUCTION;

EID: 84884678258     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2013.07.011     Document Type: Article

References (50)

1. Ali B.H., Blunden G., Tanira M.O., Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem. Toxicol. 2008, 46:409-420.
2. Baliga M.S., Haniadka R., Pereira M.M., D'Souza J.J., Pallaty P.L., Bhat H.P., Popuri S. Update on the chemopreventive effects of ginger and its phytochemicals. Crit. Rev. Food Sci. Nutr. 2011, 51:499-523.
3. Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T. Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells-evidence for cullin dimerization. Cell. Signal. 2007, 19:1071-1080.
4. Clark I.M., Swingler T.E., Sampieri C.L., Edwards D.R. The regulation of matrix metalloproteinases and their inhibitors. Int. J. Biochem. Cell Biol. 2008, 40:1362-1378.
5. Dhakshinamoorthy S., Porter A.G. Nitric oxide-induced transcriptional up-regulation of protective genes by Nrf2 via the antioxidant response element counteracts apoptosis of neuroblastoma cells. J. Biol. Chem. 2004, 279:20096-20107.
6. Dinkova-Kostova A.T., Massiah M.A., Bozak R.E., Hicks R.J., Talalay P. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:3404-3409.
7. Dinkova-Kostova A.T., Holtzclaw W.D., Kensler T.W. The role of Keap1 in cellular protective responses. Chem. Res. Toxicol. 2005, 18:1779-1791.
8. Dinkova-Kostova A.T., Liby K.T., Stephenson K.K., Holtzclaw W.D., Gao X., Suh N., Williams C., Risingsong R., Honda T., Gribble G.W., Sporn M.B., Talalay P. Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:4584-4589.
9. Dugasani S., Pichika M.R., Nadarajah V.D., Balijepalli M.K., Tandra S., Korlakunta J.N. Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol. J. Ethnopharmacol. 2010, 127:515-520.
10. Eyles J., Puaux A.L., Wang X., Toh B., Prakash C., Hong M., Tan T.G., Zheng L., Ong L.C., Jin Y., Kato M., Prévost-Blondel A., Chow P., Yang H., Abastado J.P. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J. Clin. Invest. 2010, 120:2030-2039.
11. Gan F.F., Nagle A.A., Ang X., Ho O.H., Tan S.H., Yang H., Chui W.K., Chew E.H. Shogaols at proapoptotic concentrations induce G(2)/M arrest and aberrant mitotic cell death associated with tubulin aggregation. Apoptosis 2011, 16:856-867.
12. Gan F.F., Kaminska K.K., Yang H., Liew C.Y., Leow P.C., So C.L., Tu Ngoc L.L., Roy A., Yap C.W., Kang T.S., Chui W.K., Chew E.H. Identification of Michael acceptor-centric pharmacophores with substituents that yield strong thioredoxin reductase inhibitory character correlated to antiproliferative activity. Antioxid. Redox Signal. 2013, (Epub ahead of print).
13. Ghosh S., Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature 1990, 344:678-682.
14. Gullett N.P., Ruhul Amin A.R., Bayraktar S., Pezzuto J.M., Shin D.M., Khuri F.R., Aggarwal B.B., Surh Y.J., Kucuk O. Cancer prevention with natural compounds. Semin. Oncol. 2010, 37:258-281.
15. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
16. Hayes J.D., McMahon M., Chowdhry S., Dinkova-Kostova A.T. Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway. Antioxid. Redox Signal. 2010, 13:1713-1748.
17. Hüsemann Y., Geigl J.B., Schubert F., Musiani P., Meyer M., Burghart E., Forni G., Eils R., Fehm T., Riethmüller G., Klein C.A. Systemic spread is an early step in breast cancer. Cancer Cell 2008, 13:58-68.
18. Hussain S.P., Harris C.C. Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer 2007, 121:2373-2380.
19. Jolad S.D., Lantz R.C., Solyom A.M., Chen G.J., Bates R.B., Timmermann B.N. Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production. Phytochemistry 2004, 65:1937-1954.
20. Jolad S.D., Lantz R.C., Chen G.J., Bates R.B., Timmermann B.N. Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production. Phytochemistry 2005, 66:1614-1635.
21. Kelly V.P., Ellis E.M., Manson M.M., Chanas S.A., Moffat G.J., McLeod R., Judah D.J., Neal G.E., Hayes J.D. Chemoprevention of aflatoxin B1 hepatocarcinogenesis by coumarin, a natural benzopyrone that is a potent inducer of aflatoxin B1-aldehyde reductase, the glutathione S-transferase A5 and P1 subunits, and NAD(P)H:quinone oxidoreductase in rat liver. Cancer Res. 2000, 60:957-969.
22. Khor T.O., Huang M.T., Kwon K.H., Chan J.Y., Reddy B.S., Kong A.N. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Res. 2006, 66:11580-11584.
23. Khor T.O., Huang M.T., Prawan A., Liu Y., Hao X., Yu S., Cheung W.K., Chan J.Y., Reddy B.S., Yang C.S., Kong A.N. Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer. Cancer Prev. Res. 2008, 1:187-191.
24. Klaunig J.E., Kamendulis L.M. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 2004, 44:239-267.
25. Kundu J.K., Surh Y.J. Nrf2-Keap1 signaling as a potential target for chemoprevention of inflammation-associated carcinogenesis. Pharm. Res. 2010, 27:999-1013.
26. Kundu J.K., Na H.K., Surh Y.J. Ginger-derived phenolic substances with cancer preventive and therapeutic potential. Forum Nutr. 2009, 61:182-192.
27. Levy A.S., Simon O., Shelly J., Gardener M. 6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant. BMC Pharmacol. 2006, 6:12.
28. Li Y.J., Takizawa H., Azuma A., Kohyama T., Yamauchi Y., Takahashi S., Yamamoto M., Kawada T., Kudoh S., Sugawara I. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice. Clin. Immunol. 2008, 128:366-373.
29. Ling H., Yang H., Tan S.H., Chui W.K., Chew E.H. 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation. Br. J. Pharmacol. 2010, 161:1763-1777.
30. Liu H., Dinkova-Kostova A.T., Talalay P. Coordinate regulation of enzyme markers for inflammation and for protection against oxidants and electrophiles. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:15926-15931.
31. Loboda A., Jazwa A., Grochot-Przeczek A., Rutkowski A.J., Cisowski J., Agarwal A., Jozkowicz A., Dulak J. Heme oxygenase-1 and the vascular bed: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal. 2008, 10:1767-1812.
32. Luo Y., Eggler A.L., Liu D., Liu G., Mesecar A.D., van Breemen R.B. Sites of alkylation of human Keap1 by natural chemoprevention agents. J. Am. Soc. Mass Spectrom. 2007, 18:2226-2232.
33. McMahon M., Itoh K., Yamamoto M., Hayes J.D. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J. Biol. Chem. 2003, 278:21592-21600.
34. McMahon M., Lamont D.J., Beattie K.A., Hayes J.D. Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:18838-18843.
35. Méndez-Acuña L., Di Tomaso M.V., Palitti F., Martínez-López W. Histone post-translational modifications in DNA damage response. Cytogenet. Genome Res. 2010, 128:28-36.
36. Nelson A.R., Fingleton B., Rothenberg M.L., Matrisian L.M. Matrix metalloproteinases: biologic activity and clinical implications. J. Clin. Oncol. 2000, 18:1135-1149.
37. Nievergelt A., Marazzi J., Schoop R., Altmann K.H., Gertsch J. Ginger phenylpropanoids inhibit IL-1beta and prostanoid secretion and disrupt arachidonate-phospholipid remodeling by targeting phospholipases A2. J. Immunol. 2011, 187:4140-4150.
38. Osburn W.O., Yates M.S., Dolan P.D., Chen S., Liby K.T., Sporn M.B., Taguchi K., Yamamoto M., Kensler T.W. Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice. Toxicol. Sci. 2008, 104:218-227.
39. Pan M.H., Hsieh M.C., Hsu P.C., Ho S.Y., Lai C.S., Wu H., Sang S., Ho C.T. 6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Mol. Nutr. Food Res. 2008, 52:1467-1477.
40. Ramos-Gomez M., Kwak M.K., Dolan P.M., Itoh K., Yamamoto M., Talalay P., Kensler T.W. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:3410-3415.
41. Steeg P.S. Tumor metastasis: mechanistic insights and clinical challenges. Nat. Med. 2006, 12:895-904.
42. Steinmetz K.A., Potter J.D. Vegetables, fruit, and cancer prevention: a review. J. Am. Diet. Assoc. 1996, 96:1027-1039.
43. Surh Y. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat. Res. 1999, 428:305-327.
44. Surh Y.J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 2003, 3:768-780.
45. Talalay P., De Long M.J., Prochaska H.J. Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis. Proc. Natl. Acad. Sci. U. S. A. 1988, 85:8261-8265.
46. Terry P., Giovannucci E., Michels K.B., Bergkvist L., Hansen H., Holmberg L., Wolk A. Fruit, vegetables, dietary fiber, and risk of colorectal cancer. J. Natl. Cancer Inst. 2001, 93:525-533.
47. Viatour P., Merville M.P., Bours V., Chariot A. Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem. Sci. 2005, 30:43-52.
48. Wattenberg L.W. Chemoprevention of cancer. Cancer Res. 1985, 45:1-8.
49. Wei Q.Y., Ma J.P., Cai Y.J., Yang L., Liu Z.L. Cytotoxic and apoptotic activities of diarylheptanoids and gingerol-related compounds from the rhizome of Chinese ginger. J. Ethnopharmacol. 2005, 102:177-184.
50. Wu H., Hsieh M.C., Lo C.Y., Liu C.B., Sang S., Ho C.T., Pan M.H. 6-Shogaol is more effective than 6-gingerol and curcumin in inhibiting 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice. Mol. Nutr. Food Res. 2010, 54:1296-1306.