Crocetin suppresses the growth and migration in HCT-116 human colorectal cancer cells by activating the p-38 MAPK signaling pathway

藏红花酸通过激活 p-38 MAPK 信号通路抑制 HCT-116 人结直肠癌细胞的生长和迁移

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作者:Esmaeil Khajeh, Yousef Rasmi, Fatemeh Kheradmand, Hassan Malekinejad, Pornanong Aramwit, Ehsan Saboory, Behrokh Daeihassani, Mahdieh Nasirzadeh

Background and purpose

Crocetin is a natural antioxidant that is found in the crocus flower and Gardenia jasminoides (fruit). Previous studies have reported its anticancer activity both in vivo and in vitro. 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) in vitro. Experimental approach: 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/

Purpose

Crocetin is a natural antioxidant that is found in the crocus flower and Gardenia jasminoides (fruit). Previous studies have reported its anticancer activity both in vivo and in vitro. 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) in vitro. Experimental approach: 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 (P < 0.001). Crocetin prevented migration of HCT-116 cells (P < 0.05) and suppressed VEGF and MMP-9 mRNA expression (P < 0.001) and increased phosphorylation of p38 (MAPK; P < 0.001). However, no significant change in the phosphorylation of FAK was observed.

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