Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species

Ullah, Mohammad Fahad; Ahmad, Aamir; Zubair, Haseeb; Khan, Husain Yar; Wang, Zhiwei; Sarkar, Fazlul H.; Hadi, S. M.

doi:10.1002/mnfr.201000329

Cited by 89 publications

(72 citation statements)

References 27 publications

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“…13 Dietary genistein has also been reported to reduce chemical-induced prostate cancer 14 and colon cancer 15,16 in rats. In vitro studies conducted in different cancer cell lines confirmed that by affecting various cellular targets, including several critical tumor suppressor genes, genistein treatment repressed cancer cell proliferation, [17][18][19] induced apoptosis [19][20][21] and led to cell cycle arrest. [22][23][24] However, the mechanism behind the ability of genistein to modulate the expression of tumor-promoting and tumor-suppressing genes during cancer development remains unclear.…”

Section: Genistein An Epigenome Modifier During Cancer Preventionmentioning

confidence: 90%

Genistein, an epigenome modifier during cancer prevention

Zhang

Chen

2011

Epigenetics

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Dietary compounds have been observed to have a great potential to regulate the epigenome, which is disrupted and reprogrammed during carcinogenesis. Because of their close association with cancer development, DNA methylation patterns have been used as a crucial marker for the study of cancer-related epigenetics. There is immense evidence indicating that dietary components play a critical role in cancer development. Genistein, one of the soy-derived bioactive isoflavones, affects tumorigenesis through epigenetic regulations. By modulating chromatin configuration and DNA methylation, genistein activates tumor suppressor genes and affects cancer cell survival. Here, we summarize and discuss both in vitro and in vivo studies in the field that investigate the effect of genistein on histone modifications and DNA methylation. The promising role of genistein in cancer prevention and therapeutic applications will be discussed from an epigenetic point of view.

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Section: Genistein An Epigenome Modifier During Cancer Preventionmentioning

confidence: 90%

Genistein, an epigenome modifier during cancer prevention

Zhang

Chen

2011

Epigenetics

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“…3,4 Genistein (4′,5,7-trihydroxyisoflavone, Figure 1) is one of the most abundant and best studied soy isoflavones and has received great attention for its many physiological functions, including potential antitumor activity. 5,6 Recent studies have indicated that genistein could inhibit tumor cell growth and proliferation, arrest cell cycle at G2/M phase, suppress tumor migration, invasion, and angiogenesis, and induce apoptosis and autophagocytosis. [7][8][9][10][11] However, the clinical use of genistein for cancer therapy was hindered by its poor water solubility and oral bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

Zhang¹,

Gan²,

Zeng³

et al. 2015

IJN

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Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS- b -PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS- b -PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS- b -PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS- b -PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS- b -PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

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“…These beneficial effects are considered to be particularly manifest in the lower risk of breast cancer reported for Asian women who consume soy-based foods as part of their regular diets beginning in early life (Korde et al 2009;Dong and Qin 2011). We Dave et al 2005;Su and Simmen 2009;Simmen 2010, 2011;Montales et al 2012) and others (Ullah et al 2011;Anastasius et al 2009;Kazi et al 2003;Vinall et al 2007) have shown that specific bioactive components of soy foods function by regulating cellular networks and pathways that promote apoptosis, inhibit proliferation, induce differentiation, and suppress inflammation, to collectively hinder tumor development and growth.…”

Section: Introductionmentioning

confidence: 99%

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

Pabona

Dave

et al. 2012

Genes Nutr

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Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and b-catenin nonnuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/ progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits.

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Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species

Cited by 89 publications

References 27 publications

Genistein, an epigenome modifier during cancer prevention

Genistein, an epigenome modifier during cancer prevention

Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

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