Influence of Genistein Isoflavone on Matrix Metalloproteinase-2 Expression in Prostate Cancer Cells

Kumi-Diaka, J.; Hassanhi, Manzur; Merchant, Kendra; Horman, Vanessa

doi:10.1089/jmf.2006.9.491

Cited by 35 publications

(23 citation statements)

References 36 publications

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“…30) Several MMP inhibitors have been identified from natural sources such as resveratrol, 31) theaflavins, 32) catechins, 33) curcumin [34][35][36] and genistein. 37) In this study, we showed that anethole inhibited the activity of MMP-2 and -9 and simultaneously increased the activity of TIMP-1 in HT 1080 cells. The data suggest that anethole possesses the antimetastatic activity and is a potent drug for anti-cancer treatment.…”

Section: Discussionmentioning

confidence: 60%

Anethole Exerts Antimetatstaic Activity via Inhibition of Matrix Metalloproteinase 2/9 and AKT/Mitogen-Activated Kinase/Nuclear Factor Kappa B Signaling Pathways

Choo

Rhee

Jeong

et al. 2011

Biological & Pharmaceutical Bulletin

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Anethole is known to possess anti-inflammatory and anti-tumor activities and to be a main constituent of fennel, anise, and camphor. In the present study, we evaluated anti-metastatic and apoptotic effects of anethole on highly-metastatic HT-1080 human fibrosarcoma tumor cells. Despite weak cytotoxicity against HT-1080 cells, anethole inhibited the adhesion to Matrigel and invasion of HT-1080 cells in a dose-dependent manner. Anethole was also able to down-regulate the expression of matrix metalloproteinase (MMP)-2 and -9 and up-regulate the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1. The similar inhibitory effect of anethole on MMP-2 and -9 activities was confirmed by zymography assay. Furthermore, anethole significantly decreased mRNA expression of urokinase plasminogen activator (uPA), but not uPA receptor (uPAR). In addition, anethole suppressed the phosphorylation of AKT, extracellular signal-regulated kinase (ERK), p38 and nuclear transcription factor kappa B (NF-k kB) in HT-1080 cells. Taken together, our findings indicate that anethole is a potent anti-metastatic drug that functions through inhibiting MMP-2/9 and AKT/mitogen-activated protein kinase (MAPK)/NF-k kB signal transducers.

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Section: Discussionmentioning

confidence: 60%

Anethole Exerts Antimetatstaic Activity via Inhibition of Matrix Metalloproteinase 2/9 and AKT/Mitogen-Activated Kinase/Nuclear Factor Kappa B Signaling Pathways

Choo

Rhee

Jeong

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Gn-induced decrease in MMP-2 expression levels in cancer cells has been reported previously. 39 MMP-2 expression in cancer cells has been associated with active invasion and metastasis of many human cancer cells. This indicates the potential chemopreventive significance of Gn-Se combination treatment as observed in the present studies, especially if this could be extrapolated into in vivo studies in PC3/LNCaP animal models.…”

Section: Discussionmentioning

confidence: 99%

Genistein-Selenium Combination Induces Growth Arrest in Prostate Cancer Cells

Kumi-Diaka

Merchant

Haces

et al. 2010

Journal of Medicinal Food

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The prognosis for patients with metastasized prostate cancer is still poor, despite conventional aggressive therapeutic modalities. Several in vitro studies together with animal models and epidemiological studies have indicated that phytochemicals can be antitumorigenic and may be protective against human cancers. However, the potential antitumor effects of genistein isoflavone, a widely studied nutrient phytochemical, have been equivocal. In this study, we investigated the effects of genistein-selenium (Gn-Se) combination on chemosensitivity and matrix metalloproteinase-2 (MMP-2) expression levels in PC3 (hormone-independent) and LNCaP (hormone-dependent) prostate cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium staining and ATP bioassay showed that genistein, selenium, and Gn-Se combination significantly inhibited growth of LNCaP and PC3 cells in a dose- and time-dependent manner, independent of hormonal status, and with no significant differences in chemosensitivity between LNCaP and PC3. Gn-Se combination induced significantly the greatest growth inhibition in both cell lines. Growth inhibition was through apoptosis induction. The treatment-induced apoptotic cascades are caspase-dependent, with evidence of an alternative non-caspase pathway(s). Treatment also induced a dose- and time-dependent decrease in MMP-2 expression levels in PC3 and LNCaP with no significant differences between the two cells. Gn-Se combination induced the greatest depression in MMP-2. Overall, none of the treatment modalities had any significant inhibitory effect in normal prostate epithelial cells. The data obtained from the present study indicate that Gn-Se combination may have chemopreventive value and/or may be adjuvant to standard therapy for prostate tumors independent of hormonal status. MMP-2 expression in cancer cells has been associated with active invasion and metastasis.

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“…Moreover, genistein also blocked VEGF/bFGF-induced uPA and PA inhibitor-1 expression. Later, Kumi-Diaka et al [100] also documented inhibition of MMP-2 expression in cells treated with genistein. Additionally, genistein reduced the mRNA level of several MMPs including MMP-2, MMP-3, MMP-13, and MMP-15 [101].…”

Section: Antiangiogenic Effect Of Soy Isoflavonoidsmentioning

confidence: 99%

Soy and Breast Cancer: Focus on Angiogenesis

Varinská

Gál

Mojžišová

et al. 2015

IJMS

162

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Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

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Influence of Genistein Isoflavone on Matrix Metalloproteinase-2 Expression in Prostate Cancer Cells

Cited by 35 publications

References 36 publications

Anethole Exerts Antimetatstaic Activity via Inhibition of Matrix Metalloproteinase 2/9 and AKT/Mitogen-Activated Kinase/Nuclear Factor Kappa B Signaling Pathways

Anethole Exerts Antimetatstaic Activity via Inhibition of Matrix Metalloproteinase 2/9 and AKT/Mitogen-Activated Kinase/Nuclear Factor Kappa B Signaling Pathways

Genistein-Selenium Combination Induces Growth Arrest in Prostate Cancer Cells

Soy and Breast Cancer: Focus on Angiogenesis

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