Crocin inhibits the migration, invasion, and epithelial‐mesenchymal transition of gastric cancer cells via miR‐320/KLF5/HIF‐1α signaling

Abstract

The biological activities of crocin, one of the main bioactive compounds of saffron, include anti‐inflammatory, antioxidant, antidepressant, and anticancer effects. Crocin has been shown to trigger the apoptosis of gastric cancer cells, but its effect on the metastasis of gastric cancer cells remains unclear. Krüppel‐like factor 5 (KLF5) and hypoxia‐inducible factor‐1α (HIF‐1α) are important transcription factors in the development of gastric cancer. KLF5 and HIF‐1α expression were analyzed in gastric cancer tissues and cells. Following exposure to crocin, AGS and HGC‐27 gastric cancer cells were assessed with regard to migration, invasion, and epithelial‐mesenchymal transition (EMT) as well as the expression of KLF5, HIF‐1α, and microRNA‐320 (miR‐320). The miR‐320/KLF5/HIF‐1α signaling pathway became the focus for further investigation of the mechanism of crocin in gastric cancer cell migration, invasion, and EMT. KLF5 and HIF‐1α expression were elevated in gastric cancer tissues and cells, and KLF5 expression was positively correlated with the HIF‐1α level in gastric cancer tissues. Crocin was associated with reduced expression of KLF5 and HIF‐1α, whereas miR‐320 expression was increased. Crocin also inhibited the migration, invasion, and EMT of gastric cancer cells. Upregulation of KLF5 attenuated crocin's function and elevated HIF‐1α expression. Dual‐luciferase reporter assay demonstrated that KLF5 was a target gene of miR‐320. Crocin modulated KLF5 expression via elevation of miR‐320 expression. In conclusion, crocin inhibits the EMT, migration, and invasion of gastric cancer cells, and this activity is mediated through miR‐320/KLF5/HIF‐1α signaling.

Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma

“…In previous studies, the effect of saffron extracts has been poorly investigated in cancer and there is no study on osteosarcoma. Consistent with our observations, crocin, an active constituent of saffron, was shown to impair migration and invasion capacities as well as epithelial–mesenchymal transition (EMT) of HGC‐27 gastric cancer cells . Likewise, crocetin, another bio‐active compound found in saffron, was also reported to inhibit migratory capacities of retinal pigment epithelial cells .…”

“…Consistent with our observations, crocin, an active constituent of saffron, was shown to impair migration and invasion capacities as well as epithelial-mesenchymal transition (EMT) of HGC-27 gastric cancer cells. [18] Likewise, crocetin, another bio-active compound found in saffron, was also reported to inhibit migratory capacities of retinal pigment epithelial cells. [19] In contrast, anther extract of saffron has no effect on migration capacity of HCT 116 colorectal cancer cells.…”

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

“…Crocin is a key bioactive compound with well known anti-inflammatory, anti-oxidant, and anti-cancer effects. In GC, crocin has been found to suppress the migration, invasion, and epithelial-to-mesenchymal transition (EMT) of GC cells by modulating miR-320/KLF5/HIF-1α signaling [28]. Analysis of clinical GC samples revealed that both KLF5 and HIF-1α expression are upregulated in GC tissues and that KLF5 expression is positively correlated with HIF-1α expression.…”

“…Promotes apoptosis and reduces cell invasion by regulating HIF-1α HIF-1α [23] miR-186 Directly regulates HIF-1α and inhibits cell proliferation HIF-1α [24] miR-143 Directly regulates HIF-1α HIF-1α, ZEB2-AS1 [25] PVT1 Enhances multidrug resistance and is associated with lymph node metastasis HIF-1α, MDR1, MRP, mTOR [26,27] miR-320 Upregulated by crocin and regulates HIF-1α by inhibiting KLF5 KLF5 [28] miR-210…”

Exosomal microRNA‑210 is a potentially non‑invasive biomarker for the diagnosis and prognosis of glioma

“…A range of miRNAs has been reported as tumor suppressors or oncogenes for the irreplaceable mechanism in tumor initiation and progression, and as therapeutic targets (10,11). Increasing evidence supports the idea that aberrant miRNA expression serves important roles in tumor hypoxia and is associated with HIF-1α (12,13). HIF-1α is involved in multidrug resistance by regulating miR-27 in gastric cancer cells (14).…”