Faculty of Medicine, Department of Medical Biology, Bezmialem Vakif University, Istanbul, Turkey.
Faculty of Health Sciences, Department of Child Development, University of Health Sciences, Istanbul, Turkey.
J Food Biochem. 2019 Aug;43(8):e12951. doi: 10.1111/jfbc.12951. Epub 2019 Jun 24.
This study examined the response of PC-3 cells to physiological (0.5, 2.5, 5, 10 μM) and pharmacological (50 μM) concentrations of genistein which is a main bioactive compound in soy. Following 48 hr genistein treatment, cell-based assays and genome-wide microarray were performed. It was evidenced that maximal physiologically achievable concentrations of genistein (0.5-10 μM) lead to significant increase in cell viability (p < 0.05) and decrease in migration at 0.5 μM (p = 0.000) and 10 μM (p = 0.001). The highest percentage of apoptotic cells was obtained at 50 μM. Microarray analysis gave the most critical pathways such as cell cycle regulation and proliferation, tumorigenesis, DNA damage and repair, stress response, and apoptosis. Physiological concentrations (≤10 μM) induced activation of CDKs, MAPKs, and RPSKs, while high concentrations of genistein (>10 μM) appeared to have a novel mechanism of action, specifically down-regulating TGF-β by decreasing specifically SMAD 2/3,4 which are in the downstream TGF-β signaling cascade. PRACTICAL APPLICATIONS: This study highlights for the first time that maximal physiologically achievable concentrations of genistein (0.5-10 μM) have proliferative effects evidenced by alterations in global gene expression patterns of PC-3 cells. Our results particularly represent a closer examination of dietary genistein consumption for the prevention and/or treatment of cancer that maximal physiologically achievable concentrations of genistein could have detrimental effects on individuals with prostate cancer. Further studies as in vivo would be necessary to remove shadows on the effect of genistein on prostate cancer progression.
本研究考察了 PC-3 细胞对生理浓度（0.5、2.5、5、10 μM）和药理浓度（50 μM）染料木黄酮（大豆中的主要生物活性化合物）的反应。经过 48 小时的染料木黄酮处理后，进行了基于细胞的测定和全基因组微阵列分析。结果表明，生理上可达到的最大浓度（0.5-10 μM）的染料木黄酮显著增加细胞活力（p < 0.05），并在 0.5 μM（p = 0.000）和 10 μM（p = 0.001）时降低迁移率。在 50 μM 时获得了最高比例的凋亡细胞。微阵列分析给出了最关键的途径，如细胞周期调节和增殖、肿瘤发生、DNA 损伤和修复、应激反应和细胞凋亡。生理浓度（≤10 μM）诱导 CDK、MAPK 和 RPSK 的激活，而高浓度的染料木黄酮（>10 μM）似乎具有一种新的作用机制，特别是通过降低 TGF-β信号级联下游的 SMAD 2/3、4，特异性地下调 TGF-β。
本研究首次强调，生理上可达到的最大浓度（0.5-10 μM）的染料木黄酮具有增殖作用，这表现在 PC-3 细胞的全基因表达模式的改变上。我们的研究结果特别代表了对饮食中染料木黄酮摄入用于预防和/或治疗癌症的更深入研究，因为生理上可达到的最大浓度的染料木黄酮可能对患有前列腺癌的个体产生有害影响。需要进一步的体内研究来消除染料木黄酮对前列腺癌进展影响的不确定性。
