crocin and Stomach-Neoplasms

Crocin is one of the substantial constituents of saffron extract. It has multiple clinical effects including anti-cancer effects. The development of the multidrug resistance (MDR) phenotype is one of the principal causes of cancer chemotherapy failure. The multidrug resistance protein 1 (MDR1) is one of the MDR-related protein and is often overexpressed in different cancers. In the present study, we aimed to evaluate the influence of crocin on the expression and function of MDR1 protein in EPG85-257 and EPG85-257RDB gastric cancer cell lines.. The cytotoxicity effect of crocin was evaluated by the MTT assay. The impacts of crocin on the expression and function of MDR1 were assessed by Real-time RT-PCR and MTT assay, respectively.. The results demonstrated that crocin decreased cell viability in a dose-dependent manner with higher intensity on the EPG85-257 than the EPG85-257RDB cells. Crocin did not make any significant changes in the MDR1 gene expression level in EPG85-257 and EPG85-257RDB cell lines. In contrast, crocin increased doxorubicin cytotoxicity in drug-resistant cells, which might be induced by reduced MDR1 activity.. In summary, although crocin did not affect mRNA expression of MDR1, results of MTT assay suggest that it might inhibit the MDR1 function.

Topics: Antibiotics, Antineoplastic; Apoptosis; ATP Binding Cassette Transporter, Subfamily B; Carotenoids; Cell Proliferation; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Stomach Neoplasms; Tumor Cells, Cultured

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.

Topics: Carotenoids; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kruppel-Like Transcription Factors; Male; MicroRNAs; Middle Aged; Signal Transduction; Stomach Neoplasms

This study aimed to investigate the efficacy of crocin alone and in combination with cisplatin in the therapy of gastric carcinoma cells. In this study, human gastric carcinoma cell line BGC-823 was purchased and maintained in standard condition. Crocin, cisplatin and crocin plus cisplatin diluted to different concentrations were added into medium, respectively. MTT assay and flow cytometry were performed to test the anti-proliferation effects and apoptosis rates of cells, respectively. In addition, quantitative RT-PCR was used to detect the mRNA expression of apoptosis-related genes, such as p53, Bax and Bcl-2. After treated with different concentrations of crocin, the inhibition ratio and apoptosis rate of BGC-823 cells were not significantly changed. However, the tumor cell inhibition ratio and apoptosis rate in crocin plus cisplatin group were significantly higher than that in cisplatin, crocin and control group (p<0.05). The treatment of crocin plus cisplatin significantly increased the expression of p53 and Bax (p< 0.05), and significantly decreased the Bcl-2 expression (p<0.05). Collectively, our data demonstrated for the first time that crocin plus cisplatin may be used as a new anticancer drug for the treatment of gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Carotenoids; Cell Line, Tumor; Cell Proliferation; Cisplatin; Dose-Response Relationship, Drug; Humans; Signal Transduction; Stomach Neoplasms

We previously showed the anticancer property of crocin, a carotenoid isolated and purified from saffron against chemical-induced gastric and breast cancer in rats. In this study, the mechanism of crocin action was investigated in the gastric adenocarcinoma (AGS) cells in comparison with human normal fibroblast skin cells (HFSF-PI3). Crocin revealed a dose- and time-dependent cytotoxic effect against an AGS cell line, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Crocin-induced apoptosis was evidenced by flow cytometry and measuring caspase activity. The increased sub-G1 population and activated caspases in the treated AGS cells confirmed its anticancer effect. Expression of both Bax and Bcl-2 was determined using a semiquantitative reverse transcriptase-polymerase chain reaction and Western blot in these cells before and after treatment with crocin. Apoptosis was significantly stimulated as indicated by increasing the Bax/Bcl-2 ratio after crocin treatment. All of the above-mentioned parameters remained normal in HFSF-PI3 treated with crocin. These data are providing insight into the molecular mechanisms underlying the crocin-induced apoptosis in the AGS cells, rendering it as the potential anticancer agent.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Carotenoids; Caspases; Cell Line, Tumor; Cells, Cultured; Drug Evaluation, Preclinical; Enzyme Activation; Free Radical Scavengers; Humans; Proto-Oncogene Proteins c-bcl-2; Stomach Neoplasms; Up-Regulation