Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

Park, Kyoung-Sook;Choi, Kyu-Sam;Kim, Hye-Mee;Kim, Kwang-Bae;Lee, Mi-Hee;Lee, Je-Ho;Kim Rim, Jean Chinock

  • Published : 20090600
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Abstract

During carcinogenesis, NF-${\kappa}B$ mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-${\kappa}B$ has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the I${\kappa}B$ kinase (IKK) complex that plays a central role in NF-${\kappa}B$ activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[$\alpha$]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P ＜ 0.05), and extended the latency period of tumor development (8.07 ${\pm}$ 0.92 weeks) compared to control diet animals (10.80 ${\pm}$ 1.30; P ＜ 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-${\kappa}B$ activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.

Keywords

References

  1. Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbenz(a) anthracene - induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappa B, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res 2002;62:4945-54
  2. Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett 2008;269:226-42 https://doi.org/10.1016/j.canlet.2008.03.052
  3. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996;274:782-4 https://doi.org/10.1126/science.274.5288.782
  4. Bharti AC, Aggarwal BB. Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol 2002;64:883-8 https://doi.org/10.1016/S0006-2952(02)01154-1
  5. Broemer M, Krappmann D, Scheidereit C. Requirement of Hsp90 activity for Ikappa B kinase (IKK) biosynthesis and for constitutive and inducible IKK and NF-kappaB activation. Oncogene 2004;23:5378-86 https://doi.org/10.1038/sj.onc.1207705
  6. Chen G, Cao P, Goeddel DV. TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol Cell 2002;9:401-10 https://doi.org/10.1016/S1097-2765(02)00450-1
  7. Garg A, Aggarwal BB. Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia 2002;16:1053-68 https://doi.org/10.1038/sj.leu.2402482
  8. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 2002;109 Suppl:S81-96 https://doi.org/10.1016/S0092-8674(02)00703-1
  9. Karin M. NF-kB and cancer: Mechanisms and targets. Molecular Carcinogenesis 2006;45:355-61 https://doi.org/10.1002/mc.20217
  10. Kim SE, Kim HH, Kim JY, Kang YI, Woo HJ, Lee HJ. Anticancer activity of hydrophobic peptides from soy proteins. Biofactors 2000;12:151-5 https://doi.org/10.1002/biof.5520120124
  11. Lee KB, Lee JS, Park JW, Huh TL, Lee YM. Low energy proton beam induces tumor cell apoptosis through reactive oxygen species and activation of caspases. Exp Mol Med 2008;38:553-64 https://doi.org/10.3858/emm.2008.40.1.118
  12. Lee M, Choi I, Park K. Activation of stress signaling molecules in bat brain during arousal from hibernation. J Neurochemistry 2002;82:867-73 https://doi.org/10.1046/j.1471-4159.2002.01022.x
  13. Maloney A, Workman P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther 2002;2:3-24 https://doi.org/10.1517/14712598.2.1.3
  14. Messina MJ, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991;83:541-6 https://doi.org/10.1093/jnci/83.8.541
  15. Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 1994;21:113-31 https://doi.org/10.1080/01635589409514310
  16. Nam D, Song S, Park K, Kim M, Suh Y, Lee J, Kim S, Hong S, Shin H, Park K, Eoh W, Kim J. Clinical significance of molecular genetic changes in sporadic invasive pituitary adenomas. Exp. Mole. Med. 2001;33:111-6 https://doi.org/10.1038/emm.2001.20
  17. Neckers L, Ivy SP. Heat shock protein 90. Curr Opin Oncol 2003;15:419-24 https://doi.org/10.1097/00001622-200311000-00003
  18. Park J, Park K, Kim S, Lee JH. Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer cell line OVCAR3. Biochem Biophys Res Comm 2001;281:1234-40 https://doi.org/10.1006/bbrc.2001.4474
  19. Park K, Kim K, Rho SB, Choi K, Kim D, Oh SH, Park J, Lee SH, Lee JH. Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis. Cancer Res 2005;65:749-57
  20. Russo IH, Koszalka M, Gimotty PA, Russo J. Protective effect of chorionic gonadotropin on DMBA-induced mammary carcinogenesis. Br J Cancer 1990;62:243-7 https://doi.org/10.1038/bjc.1990.268
  21. Sarkar FH, Li Y. Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer and Metastasis Rev 2002;21:265-80 https://doi.org/10.1023/A:1021210910821
  22. Sarkar FH, Li Y. Soy isoflavones and cancer prevention. Cancer Invest 2003;21:744-57 https://doi.org/10.1081/CNV-120023773
  23. Shin ZI, Yu R, Park SA. His-His-Leu, an angiotensin I converting enzyme inhibitory peptide derived from Korean soybean paste, exerts antihypertensive activity in vivo. J Agric Food Chem 2001;49:3004-9 https://doi.org/10.1021/jf001135r
  24. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003;3:768-80 https://doi.org/10.1038/nrc1189
  25. Takayama S, Reed JC, Homma S. Heat-shock proteins as regulators of apoptosis. Oncogene 2003;22:9041-7 https://doi.org/10.1038/sj.onc.1207114
  26. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS, Jr. NF-kappa B antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998;281:1680-3 https://doi.org/10.1126/science.281.5383.1680
  27. Whitesell L, Lindquist S. HSP90 and the chaperoning of cancer. Nature Rev Cancer 2005; 5:761-72 https://doi.org/10.1038/nrc1716

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  16. Suppression of inflammatory cascade is implicated in methyl amooranin‐mediated inhibition of experimental mammary carcinogenesis vol.53, pp.12, 2009, https://doi.org/10.1002/mc.22067
  17. Trianthema portulacastrum Linn. Displays Anti-Inflammatory Responses during Chemically Induced Rat Mammary Tumorigenesis through Simultaneous and Differential Regulation of NF-κB and Nrf2 Signa vol.16, pp.2, 2009, https://doi.org/10.3390/ijms16022426
  18. Dietary Soy Peptide Enhances Thermotolerance and Survival of Juvenile Japanese Flounder, Paralichthys olivaceus vol.46, pp.2, 2009, https://doi.org/10.1111/jwas.12183
  19. Updating the research on the chemopreventive and therapeutic role of the peptide lunasin vol.98, pp.6, 2018, https://doi.org/10.1002/jsfa.8719
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