Buranrat Benjaporn, Mairuae Nootchanat, Konsue Ampa
Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand.
Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand.
Biomed Pharmacother. 2017 Jun;90:77-84. doi: 10.1016/j.biopha.2017.03.032. Epub 2017 Mar 24.
In this study we investigated how Cratoxy formosum (CF) leaf extract affects the viability and migration of human breast cancer cells including the mechanism(s) responsible. Our results showed that CF leaf extract strongly induced MCF-7 cell death in a concentration- and time-dependent manner, with IC values of 85.70±4.52μg/mL and 53.74±3.02μg/mL at 24h and 48h, respectively. Additionally, CF leaf extract potentiated the activity of 4 anticancer drugs with the greatest synergy occurring between CF and 5-FU. CF leaf extract also caused a dose-dependent decrease in colony forming ability with IC values of 36.37+1.80 μg/mL and cell migration, with IC values of 43.68±0.86μg/mL. Moreover, CF significantly induced ROS formation, increased caspase 3 activities, and reduced the mitochondrial membrane potential, leading to cancer cell apoptosis and cell death. In addition, the extract inhibited cancer cell migration at 25μg/mL by reducing MMP 2 and MMP 9 protein expression. Moreover, CF leaf extracts strongly decreased expression of the cell cycle regulatory protein Rac1 and downstream protein, cdk6. CF leaf extract significantly stimulated p21 and this correlated with a reduction in cyclin D1 protein levels. In summary, CF leaf extract can inhibit cell proliferation, induce cell apoptosis, and reduce cell migration in the MCF-7 cell line. It could also be beneficial for enhancing the activity of anticancer drugs used to treat breast cancer.
在本研究中，我们调查了台湾黄牛木（Cratoxy formosum，CF）叶提取物如何影响人乳腺癌细胞的活力和迁移，以及相关机制。我们的结果表明，CF叶提取物以浓度和时间依赖性方式强烈诱导MCF-7细胞死亡，在24小时和48小时时的IC值分别为85.70±4.52μg/mL和53.74±3.02μg/mL。此外，CF叶提取物增强了4种抗癌药物的活性，其中CF与5-氟尿嘧啶（5-FU）之间的协同作用最强。CF叶提取物还导致集落形成能力呈剂量依赖性下降，IC值为36.37+1.80μg/mL，细胞迁移能力也下降，IC值为43.68±0.86μg/mL。此外，CF显著诱导活性氧（ROS）形成，增加半胱天冬酶3活性，并降低线粒体膜电位，导致癌细胞凋亡和细胞死亡。此外，该提取物在25μg/mL时通过降低基质金属蛋白酶2（MMP 2）和基质金属蛋白酶9（MMP 9）蛋白表达来抑制癌细胞迁移。此外CF叶提取物强烈降低细胞周期调节蛋白Rac1及其下游蛋白细胞周期蛋白依赖性激酶6（cdk6）的表达。CF叶提取物显著刺激p21表达，这与细胞周期蛋白D1（cyclin D1）蛋白水平降低相关。总之，CF叶提取物可抑制MCF-7细胞系中的细胞增殖、诱导细胞凋亡并减少细胞迁移。它还可能有助于增强用于治疗乳腺癌的抗癌药物的活性。
