Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin.
ABSTRACT Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of cell-cell adhesion and an increased cell invasion. Many studies have shown the antiproliferative activities of luteolin on cancer cells. However, the effects of luteolin on invasion of cancer cells remain unclear. In this article, we show that luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. We found that Luteolin induced expression of E-cadherin through mdm2. Overexpression of mdm2 or knockdown of E-cadherin could restore invasion of PC3 cells after luteolin treatment. Luteolin inhibits mdm2 through AKT and overexpression of active AKT attenuated luteolin-induced expression of E-cadherin, suggesting that luteolin regulates E-cadherin through AKT/mdm2 pathway. The in vivo experiments showed that luteolin inhibited spontaneous lung metastasis of PC3 cells implanted onto the nude mice. These findings provide a new sight into the mechanisms that luteolin is against cancer cells, and suggest that molecular targeting of E-cadherin by luteolin may be a useful strategy for treatment of invasive prostate cancers.
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ABSTRACT: Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as "nature's power fruit". Recent research has shown that pomegranate juice (PJ) and/or pomegranate extracts (PE) significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA) doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis.International Journal of Molecular Sciences 09/2014; 15(9):14949-14966. · 2.34 Impact Factor
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ABSTRACT: Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.International Journal of Oncology 01/2014; · 2.77 Impact Factor