Procyanidins from Evening Primrose (Oenothera paradoxa) Defatted Seeds Inhibit Invasiveness of Breast Cancer Cells and Modulate the Expression of Selected Genes Involved in Angiogenesis, Metastasis, and Apoptosis

Lewandowska, Urszula; Szewczyk, Karolina; Owczarek, Katarzyna; Hrabec, Zbigniew; Podsędek, Anna; Sosnowska, Dorota; Hrabec, Elżbieta

doi:10.1080/01635581.2013.830314

Cited by 33 publications

(29 citation statements)

References 47 publications

(63 reference statements)

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“…The major proanthocyanidin in evening primrose extract are in dimer and trimer form. 23) This additional evidences confirm that proanthocyanidin in PRFR are the oligomers which might have a similar structure to the proanthocyanidin in the grape seed extract.…”

Section: Discussionsupporting

confidence: 68%

Proanthocyanidin in Red Rice Inhibits MDA-MB-231 Breast Cancer Cell Invasion via the Expression Control of Invasive Proteins

Pintha

Yodkeeree

Limtrakul

2015

Biological & Pharmaceutical Bulletin

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Proanthocyanidin is one of the main active compounds found in red jasmine rice. We previously reported that red rice extract could reduce cancer cell invasion. However, the direct effect of proanthocyanidin from red rice on the invasion of cancer cells and the exact molecular mechanism remained unclear. Here, we report for the first time that proanthocyanidin-rich fraction from red rice (PRFR) reduced the migration and invasion of MDA-MB-231 human breast cancer cells. The types of proanthocyanidin in PRFR were identified as procyanidins and prodelphinidins by acid hydrolysis. For cancer cell invasion, degradation of the extracellular matrix (ECM) is required. Treatment of the cells with PRFR reduced the expression of ECM degradation-associated proteins, including matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase, urokinase plasminogen activator, urokinase plasminogen activator receptor and plasminogen activator-1. Moreover, PRFR also reduced the activity of collagenase and MMP-9. Furthermore, PRFR significantly suppressed the expression of intercellular adhesion molecule-1 and interleukin-6. We also found that PRFR reduced the DNA-binding activity of nuclear factor kappa B (NF-κB), which is the expressed mediator of ECM degradation-associated proteins. These results suggest that proanthocyanidin from red rice mediates MDA-MB-231 breast cancer cell invasion by altering the expression of the invasion-associated proteins, possibly by targeting NF-κB activity.Key words proanthocyanidin; red rice; invasion; nuclear factor kappa B Breast cancer is a leading cause of mortality among women worldwide including in Thailand. The metastasis of breast cancer to other sites such as the liver, bones, the lungs and lymph nodes is a critical factor contributing to the increased rate of mortality in breast cancer patients.1) The metastasis of cancer cells is a complex process involving cell adhesion, migration and proteolytic degradation of the extracellular matrix (ECM). Degradation of ECM components is an important step in the metastatic process, and it is regulated by the activation of ECM degradation enzymes such as matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). 2)Several scientific studies have shown that uPA plays an important role in tumor metastasis and over-expression of uPA in breast cancer is a strong indicator of the poor prognosis.3)The uPA converts the inactive plasminogen into the active serine protease plasmin, which is involved in the degradation of ECM. The uPA system consists of uPA, the uPA receptor (uPAR), plasminogen and its inhibitor, plasminogen inhibitor types 1 and 2 (PAI-1 and -2). The binding of uPA to uPAR not only promotes cancer metastasis but also generates signal transduction that allows enhanced cell survival and migration. 3)MMPs essentially degrade all ECM components surrounding the cancer cells, allowing them to spread from the primary site. Up-regulation of several MMPs such as MMP-2, -3, -9 and membrane type-1 matrix metalloproteinases ...

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Section: Discussionsupporting

confidence: 68%

Proanthocyanidin in Red Rice Inhibits MDA-MB-231 Breast Cancer Cell Invasion via the Expression Control of Invasive Proteins

Pintha

Yodkeeree

Limtrakul

2015

Biological & Pharmaceutical Bulletin

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“…For instance, Li et al [2010] testing a polyphenol extract from Devil's Club (Oplopanax horridus) on different colorectal cancer cell lines observed that this preparation did not infl uence HT-29 proliferation at all whereas signifi cantly reduced the growth of HCT-116 cell line. Moreover, in our studies, we observed a strong inhibition of MDA-MB-231 human breast cancer cell division by the polyphenol extract from evening primrose [Lewandowska et al, 2013].…”

Section: Discussionmentioning

confidence: 64%

“…After extraction of oil the remaining defatted seeds contain polyphenolic compounds that can have benefi cial health effect. So far, the extracts obtained from defatted seeds from Oenothera paradoxa Hudziok caused a decrease of plasma cholesterol and low density lipoprotein cholesterol in rats [Bałasińska, 1998], a dose-dependent inhibition of lipid peroxidation in mouse lymphocytic leukemic L1210 cells [Bałasińska & Troszyńska, 1998] a dose-dependent inhibition of metallopeptidases activity [Kiss et al, 2008], induction of apoptosis in human skin melanoma HTB-140 cells [Jaszewska et al, 2009] and reduction of cell viability and cell invasiveness in human breast cancer MDA-MB-231 cells [Lewandowska et al, 2013].…”

Section: Introductionmentioning

confidence: 99%

Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa) Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

Szewczyk¹,

Lewandowska²,

Owczarek³

et al. 2014

Pol. J. Food Nutr. Sci.

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Key words: evening primrose, matrix metalloproteinases, cancer Evening primrose (Oenothera paradoxa Hudziok) seeds are a rich source of not only a valuable oil containing an essential fatty acid --linolenic acid (GLA) -but also polyphenols which can be obtained from the biomass remaining after oil pressing. The aim of our studies was to evaluate the infl uence of a polyphenol extract from defatted seeds of evening primrose on human colorectal adenocarcinoma Caco-2 cell proliferation and matrix metalloproteinases (MMPs) synthesis and activity. To assess the effect of evening primrose extract on Caco-2 cell proliferation, crystal violet staining and sulforhodamine B (SRB) assays were used whereas mRNA expression and activity of MMPs were evaluated by RT-PCR and gelatin zymography.The results revealed that the examined polyphenol extract had little infl uence on Caco-2 proliferation, but effectively in a time-and dose-dependent manner inhibited MMP-1, MMP-7, MMP-9 and MMP-14 mRNA synthesis induced by TNF- and TPA. Additionally, zymographic analysis revealed that after 24 h, the polyphenol extract at a concentration of 50 mol/L GAE caused a 10-fold reduction in MMP-9 synthesis. Moreover, this extract might be a potent inhibitor of MMP activity. The results showed that polyphenol extract from evening primrose inhibited PBMC-derived MMP-2 and MMP-9 enzymatic activity in dose-dependent manner. The obtained results indicate that the polyphenol extract from evening primrose seeds could be an inhibitor of proteases involved in tumor progression and metastasis.

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“…The aim of the present work was to assess the apoptotic and angiogenic activities of the procyanidin-rich EPFP towards non-invasive breast cancer cells (MCF-7) with respect to the expression of genes associated with these processes, and then to compare these results with those obtained for MDA-MB-231 cells [15].…”

Section: Introductionmentioning

confidence: 99%

“…One report, from our laboratory, examines the effect of evening primrose flavanol preparation (EPFP), a flavanol preparation obtained from defatted seeds of evening primrose, on a highly invasive breast cancer cell line (MDA-MB-231) [15]. The aim of the present work was to assess the apoptotic and angiogenic activities of the procyanidin-rich EPFP towards non-invasive breast cancer cells (MCF-7) with respect to the expression of genes associated with these processes, and then to compare these results with those obtained for MDA-MB-231 cells [15].…”

Section: Introductionmentioning

confidence: 99%

Differentiated impact of procyanidins from evening primrose on human breast cancer cells

et al. 2014

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This study examines some of the biological activities of an evening primrose flavanol preparation (EPFP) against non-invasive human breast cancer cells (MCF-7). The results are compared with those obtained for highly invasive human breast cancer cells (MDAMB-231). The results show, for the first time, that EPFP reduces MCF-7 cell number, IC50 = 75 µM gallic acid equivalents/GAE for 72 h incubation, and reduces migration to 52% of the control value at 100 µM L−1 GAE. EPFP caused favorable changes in Bcl-2/Bax mRNA ratio, which rendered MCF-7 cells more sensitive to apoptosis: the number of apoptotic cells increased 2.2-fold vs. control at 100 µM GAE. Furthermore, 100 µ M L−1 GAE EPFP caused a 1.8-fold reduction in the activity of metalloproteinase-9 (MMP-9) secreted to the culture medium by MCF-7 cells. Moreover, EPFP suppressed the expression of selected genes of matrix metalloproteinases (MMPs), a proliferation marker (Ki67), and vascular endothelial growth factor (VEGF). In conclusion, the results of this study suggest that EPFP may exhibit proapoptotic, antiproliferative, antimigratory, and antimetastatic potential towards both selected human breast cancer cell lines, which is more pronounced in the case of the highly invasive MDA-MB-231 cells.

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Procyanidins from Evening Primrose (Oenothera paradoxa) Defatted Seeds Inhibit Invasiveness of Breast Cancer Cells and Modulate the Expression of Selected Genes Involved in Angiogenesis, Metastasis, and Apoptosis

Cited by 33 publications

References 47 publications

Proanthocyanidin in Red Rice Inhibits MDA-MB-231 Breast Cancer Cell Invasion <i>via</i> the Expression Control of Invasive Proteins

Proanthocyanidin in Red Rice Inhibits MDA-MB-231 Breast Cancer Cell Invasion <i>via</i> the Expression Control of Invasive Proteins

Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa) Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

Differentiated impact of procyanidins from evening primrose on human breast cancer cells

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