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

Abstract

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/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. Conclusion and implication: 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.

Crocetin Protected Human Hepatocyte LO2 Cell From TGF-β-Induced Oxygen Stress and Apoptosis but Promoted Proliferation and Autophagy via AMPK/m-TOR Pathway

“…Saffron is a perennial herb of Crocus sativus (Iridaceae), which is not only a kind of spice but also a highly valued medicine (1,2). As a component of traditional medicine, saffron had been used as a medicinal herb for treating various ailments including cramps, asthma, liver disease, menstruation disorders, pain, and in the pathogenesis of cancer (3)(4)(5)(6)(7)(8). Crocin, crocetin, picrocrocin and safranal are the main secondary metabolites of Crocus sativus (9).…”

Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology

“…Interestingly, a recent in vitro study observed that crocin inhibits proliferation and migration of metastasis-associated in colon cancer 1 (MACC1)-expressing colorectal cells in a concentration dependent manner [123]. It is noteworthy that crocetin (800 μM) also represses growth and migration by the upregulation of p38 mitogen-activated protein kinase (MAPK) and downregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) signaling pathways in HCT-116 human colorectal cancer cells [124] as well as Wnt/b-catenin (Wingless-type/b-catenin) pathway in mouse breast carcinoma cells [125]. In addition, the combination of saffron aqueous extract and high-intensity interval training (HIIT) strategy suppress tumor growth through the upregulation of p53 and Sirtuin-1 in breast cancer cells [117].…”

Novel Set of Diarylmethanes to Target Colorectal Cancer: Synthesis, In Vitro and In Silico Studies

“…C Extracellular signal-regulated kinases (ERKs), are member of the mitogen-activated protein kinase (MAPK) involved in a series of physiological processes, such as the regulation of cell survival and proliferation as well as cell differentiation [44][45][46]. Colon tumor epithelial cells are dependent on mitogen activated protein kinase (MAPK) p38 for proliferation and survival [47,48]. We investigated the role of ERK and p38 in the observed antiproliferative effect.…”