Khajeh Esmaeil, Rasmi Yousef, Kheradmand Fatemeh, Malekinejad Hassan, Aramwit Pornanong, Saboory Ehsan, Daeihassani Behrokh, Nasirzadeh Mahdieh
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Res Pharm Sci. 2020 Nov 27;15(6):592-601. doi: 10.4103/1735-5362.301344. eCollection 2020 Dec.
Crocetin is a natural antioxidant that is found in the crocus flower and (fruit). Previous studies have reported its anticancer activity both and . In addition, crocetin suppresses the growth and migration of human colorectal cancer cells, however, its mechanism of action remains to be elucidated. Therefore, the present study investigated the molecular mechanism of crocetin effect on colorectal cancer cells (HCT-116) .
HCT-116 cells were treated with different concentrations (0, 200, 400, 600, and 800 μM) of crocetin for 24 h. The cell survival rate was measured by MTT assay. Cell migration capacity was evaluated using the wound healing assay. The expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP-9) was monitored by RT-PCR. Phosphorylation of focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) was determined using western blot.
FINDINGS/RESULTS: The proliferation of HCT-116 was inhibited by crocetin at 800 μM ( < 0.001). Crocetin prevented migration of HCT-116 cells ( < 0.05) and suppressed VEGF and MMP-9 mRNA expression ( < 0.001) and increased phosphorylation of p38 (MAPK; < 0.001). However, no significant change in the phosphorylation of FAK was observed.
These data suggested that crocetin-induced growth- and migration- suppressing effects on HCT-116 cells may partially depend on the regulation of the p38 (MAPK) signaling pathway.
藏红花素是一种存在于藏红花花和（果实）中的天然抗氧化剂。先前的研究已报道其在体内和体外均具有抗癌活性。此外，藏红花素可抑制人结肠癌细胞的生长和迁移，然而，其作用机制仍有待阐明。因此，本研究探讨了藏红花素对结肠癌细胞（HCT - 116）作用的分子机制。
用不同浓度（0、200、400、600和800 μM）的藏红花素处理HCT - 116细胞24小时。通过MTT法测定细胞存活率。使用伤口愈合试验评估细胞迁移能力。通过RT - PCR监测血管内皮生长因子（VEGF）和基质金属蛋白酶（MMP - 9）的表达水平。使用蛋白质印迹法测定粘着斑激酶（FAK）和p38丝裂原活化蛋白激酶（MAPK）的磷酸化。
800 μM的藏红花素可抑制HCT - 116的增殖（P < 0.001）。藏红花素可阻止HCT - 116细胞迁移（P < 0.05），抑制VEGF和MMP - 9 mRNA表达（P < 0.001），并增加p38（MAPK）的磷酸化（P < 0.001）。然而，未观察到FAK磷酸化有显著变化。
这些数据表明，藏红花素对HCT - 116细胞的生长和迁移抑制作用可能部分取决于p38（MAPK）信号通路的调节。
