Maggioni Daniele, Nicolini Gabriella, Rigolio Roberta, Biffi Luisa, Pignataro Lorenzo, Gaini Renato, Garavello Werner
a Department of Surgery and Translational Medicine , University of Milan-Bicocca , Monza , Italy.
Nutr Cancer. 2014;66(7):1257-67. doi: 10.1080/01635581.2014.951732. Epub 2014 Sep 25.
In this study the potential anticancer effect of 2 flavonoids, myiricetin (MYR) and naringenin (NAR) has been evaluated on an oral squamous cell carcinoma (OSCC) cell line, SCC-25, and HaCaT cells. Both the flavonoids inhibited SCC-25 cell growth, although NAR selectively affected cancer cells without impairing HaCaT cell growth. The cell proliferation inhibition by MYR and NAR was not related to apoptosis induction, but on cell cycle impairment, because a G0/G1 and a G2/M blockage was highlighted following 24 h of treatment in SCC-25 and HaCaT cells, respectively. Western blot analysis showed that MYR induced a decrease of Cyclin D1 in SCC-25 and of Cyclin B1 in HaCaT cells, while NAR negatively modulated Cyclin D1 expression in SCC-25 cells. Wound-healing and cell invasion assays demonstrated that both the flavonoids were able to reduce motility on both SCC-25 and HaCaT cells. In conclusion the results of the present study show the anticancer potential of NAR and MYR on OSCC because they exert cytostatic effect by the impairment of cell cycle progression. Moreover both the flavonoids inhibit cell migration, thus highlighting their potential effect as antimetastatic agents. Therefore, MYR and NAR appear as promising candidate as oral cancer chemopreventive agents.
在本研究中,评估了两种黄酮类化合物杨梅素(MYR)和柚皮素(NAR)对口腔鳞状细胞癌(OSCC)细胞系SCC - 25和HaCaT细胞的潜在抗癌作用。两种黄酮类化合物均抑制SCC - 25细胞生长,尽管NAR选择性地影响癌细胞而不损害HaCaT细胞生长。MYR和NAR对细胞增殖的抑制作用与诱导凋亡无关,而是与细胞周期受损有关,因为在分别处理SCC - 25和HaCaT细胞24小时后,突出显示了G0/G1期和G2/M期阻滞。蛋白质印迹分析表明,MYR导致SCC - 25细胞中细胞周期蛋白D1减少,HaCaT细胞中细胞周期蛋白B1减少,而NAR负向调节SCC - 25细胞中细胞周期蛋白D1的表达。伤口愈合和细胞侵袭试验表明,两种黄酮类化合物均能够降低SCC - 25和HaCaT细胞的运动性。总之,本研究结果显示了NAR和MYR对OSCC的抗癌潜力,因为它们通过损害细胞周期进程发挥细胞生长抑制作用。此外,两种黄酮类化合物均抑制细胞迁移,从而突出了它们作为抗转移剂的潜在作用。因此,MYR和NAR似乎是有前景的口腔癌化学预防剂候选物。