Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

Park, Kyoungsook; Choi, Kae Won; Kim, Hyemee; Kim, Kwangbae; Lee, Mi Hee; Lee, Je Ho; Rim, Jean C.

doi:10.3858/emm.2009.41.6.042

Cited by 36 publications

(27 citation statements)

References 26 publications

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“…Moreover, the tumor sections obtained from the lunasin-enriched group showed slight stromal invasion and degree of morphological aggressiveness due to the effect of this peptide contained in the soy protein preparation. Park and co-works have reported that isoflavone-deprived soy peptides prevent DMBA-induced rat mammary tumorigenesis, as well as inhibit the growth of human breast cancer MCF-7 cells in a dose-dependent manner, and induce cell death [51]. Lunasin might be responsible for the effects reported by these authors.…”

Section: Lunasin Against Breast Cancer In Vivomentioning

confidence: 74%

1997-2012: Fifteen Years of Research on Peptide Lunasin

Hernández-Ledesma¹,

Lumen²,

Hsieh³

2013

Bioactive Food Peptides in Health and Disease

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Section: Lunasin Against Breast Cancer In Vivomentioning

confidence: 74%

1997-2012: Fifteen Years of Research on Peptide Lunasin

Hernández-Ledesma¹,

Lumen²,

Hsieh³

2013

Bioactive Food Peptides in Health and Disease

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“…AKT is a serine threonine kinase downstream of PI3K, which has a large number of downstream targets implicated in survival and cell cycle regulation (32,33). The IKK complex plays a central role in NF-κB activation and has various biological effects in cancer cells (34). Constitutive activation of NF-κB is an emerging hallmark of a wide variety of tumor types, including melanoma (35).…”

Section: Discussionmentioning

confidence: 99%

The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo

et al. 2012

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Abstract. SNX-2112 is a selective heat shock protein 90 (Hsp90) inhibitor which can exert a potent anticancer activity. In this study, we investigated the effects of SNX-2112 on B16 melanoma cells in vitro and in vivo. The 3-(4,5-dimetrylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis demonstrated that SNX-2112 dosedependently inhibited the growth of B16 cells, and induced G0/ G1 cell cycle arrest and apoptosis. Western blotting revealed that SNX-2112 lead to the degradation of Hsp90 client proteins including Akt, IKKα, NF-κB, B-Raf and GSK3β. Furthermore, we assessed the antitumor effect of SNX-2112 in vivo, using a xenograft model in C57BL/6 mice. Oral administration of SNX-2112 significantly inhibited the growth of B16 tumors in mice, with a 47% inhibition observed at dose of 80 mg/kg/day for 15 days, compared to control tumors. Hematoxylin-eosin (H&E) staining of xenograft tissues showed that SNX-2112 also inhibited angiogenesis and lead to a lower blood vessel density in the tumors, compared to the control group. These findings demonstrate that SNX-2112 can exhibit a potent anticancer activity against B16 melanoma cells both in vitro and in vivo, by inhibiting cell proliferation and inducing cell cycle arrest and apoptosis in a mechanism dependent on the degradation of Hsp90 client proteins. IntroductionHsp90 is an important ATP-dependent molecular chaperone required for protein folding, as well as the assembly and maintenance of the conformational stability of a diverse range of client proteins. Hsp90 client proteins play key roles in cellular metabolism, trafficking, signal transduction, chromatin remodeling, cell growth and differentiation (1-4). Hsp90 client proteins include cell survival and proliferation regulators, such as Akt, IKK, Raf, GSK3 and NF-κB (5-7). Hsp90 is overexpressed in tumor cells compared to their normal counterparts (8), and inhibition of Hsp90 has been considered as a possible strategy for the treatment of cancer.Currently, 14 drug candidates which target Hsp90 are undergoing clinical trials for multiple indications, either as single agents or in combination therapy, including 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504) and BIIB021 (9). 17-AAG was the first Hsp90 inhibitor to undergo phase III clinical trials, and is well tolerated and has a good therapeutic efficacy. However, 17-AAG has several potential limitations, including poor solubility, limited bioavailability and unsatisfactory hepatotoxicity (10-12). This has led to efforts to identify new, safer and more effective Hsp90 inhibitors for clinical applications.SNX-2112, a selective Hsp90 inhibitor, can bind to the N-terminal adenosine triphosphate binding site of Hsp90 and can exert significant growth inhibition of various cancer cell lines both in vitro and in vivo (13,14). In our previous research, SNX-2112 displayed promising anti-tumor activity in human chronic leukemia 16). In addition, SNX-2112 is ...

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“…The use of peptide and its derivatives for the application to basic and medicinal research has been extensively studied (Bruckdorfer et al, 2004;Park et al, 2009). Synthetic combinatorial peptide libraries have been utilized successfully to discover bioactive peptides such as antimicrobial peptides (Blondelle et al, 1996), ligands for cell surface receptors (Bae et al, 2003), protein kinase inhibitors and substrates (Wu et al, 1994;Songyang et al, 1995), and peptide mimotopes of receptor binding sites (Bracci et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

Kim

Hong

et al. 2010

Exp Mol Med

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Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF-and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases.

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Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

Cited by 36 publications

References 26 publications

1997-2012: Fifteen Years of Research on Peptide Lunasin

1997-2012: Fifteen Years of Research on Peptide Lunasin

The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo

A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

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