ABSTRACT
The present study aimed to investigate the effect of apigenin on glioma cells and to explore its potential mechanism. U87 human glioma cells treated with apigenin were used in the current study. Cell Counting Kit8 solution and Annexin V-fluorescein isothiocyanate/propidium iodide Apoptosis Detection kit were used to analyze the effect of apigenin on U87 cell viability and apoptotic cell death. Reverse transcriptionquantitative polymerase chain reaction analysis was also used to determine microRNA16 (miR16) and MMP9 gene expression levels. Nuclear factorκB (NFκB) and Bcell CLL/lymphoma 2 (BCL2) protein expression levels were determined using western blot analysis. An antimiR16 plasmid was constructed and transfected into U87 cells. The current study demonstrated that apigenin significantly decreased cell viability and induced apoptotic cell death of U87 cells in a dosedependent manner. Additionally, it was demonstrated that apigenin significantly increased miR16 levels, suppressed BCL2 protein expression and suppressed the NFκB/MMP9 signaling pathway in U87 cells. Furthermore, downregulation of miR16 using the antimiR16 plasmid reversed the effect of apigenin on cell viability, BCL2 protein expression and the NFκB/MMP9 pathway in U87 cells. The results of the present study suggested that apigenin inhibits glioma cell growth through promoting miR16 and suppression of BCL2 and NF-κB/MMP-9. In conclusion, the present study demonstrated the potential anticancer effects of apigenin on glioma cells.
Subject(s)
Apigenin/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Apigenin/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Glioma/genetics , Glioma/metabolism , Humans , Signal Transduction/drug effectsABSTRACT
AIM: Quercetin affects the expressions of leptin and its receptor in human gastric cancer MGC-803 cells and JAK-STAT pathway. METHODS: The cultured MGC-803 cells were divided into three groups: CONTROL GROUP: the cultured cells without quercetin, and Quercetin group: the cultured cells with quercetin(40 µmol/L), and AG490group: the cultured cells with AG490(40 µmol/L)The expressions of Leptin, Leptin receptor and P-STAT3 were detected in protein level by immunocytochemical and Western bloting method respectively. The expressions of Leptin, Leptin receptor were detected in mRNA level by RT-PCR method. MGC-803 cell cycle was arrest by flow cytometry (FCM); MGC-803 cell apoptosis ratio by apoptotic marker An-necxinV. RESULTS: The protein expression of Leptin, Leptin receptor, P-STAT3 and the the mRNA expression of Leptin and Leptin receptor were significantly increased (P<0.05), compared with the control group.There was the rectilinear correlation relationship not only between Leptin and P-STAT3 protein(r=0.741, P<0.05) but also between Leptin receptor and P-STAT3 protein(r=0.693, P<0.05). FCM analysis showed that quercetin arrested MGC-803 cells at the G2/M phase, The ratio of apoptotic and necrosic cells increased with added quercetin concentration. CONCLUSION: Quercetin could inhibit the Proliferation of MGC-803 cells. It is probably relevant to the down-regulation the expressions of Leptin and Leptin receptor protein, Leptin mRNA and Leptin receptor mRNA by JAK-STAT pathway.
Subject(s)
Janus Kinases/metabolism , Leptin/metabolism , Quercetin/pharmacology , Receptors, Leptin/metabolism , STAT Transcription Factors/metabolism , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , Antioxidants/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Line, Tumor , Humans , Receptors, Leptin/genetics , Stomach Neoplasms/geneticsABSTRACT
AIM: To investigate the mechanism of quercetin on the inhibition of the lymphatic metastasis in human gastric cancer cells MGC-803. METHODS: Cells were divided into the control group and the quercetin (Que)-treated group. Immunohistochemistry and RT-PCR were used to detect the expression of vascular endothelial growth factor C (VEGF-C) and VEGFR-3 of human gastric cancer cells MGC-803 in response to Que. RESULTS: Que significantly decreased the expression of VEGF-C and VEGFR-3 at 40 mumol/L compared with the control group after 48 h (P<0.01). CONCLUSION: Que can down-regulate the expression of VEGF-C and VEGFR-3 in human gastric cancer cells MGC-803.
Subject(s)
Down-Regulation/drug effects , Quercetin/pharmacology , Stomach Neoplasms/genetics , Vascular Endothelial Growth Factor C/genetics , Vascular Endothelial Growth Factor Receptor-3/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Vascular Endothelial Growth Factor C/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolismABSTRACT
AIM: To study the effect of quercetin on the growth and apoptosis of human gastric carcinoma cell line MGC-803. METHODS: The measurement of inhibitory rate and apoptotic index(AI) of quercetin were done by MTT assay and TUNEL assay. The positive expression rate of P53, C-myc and P16 were detected by immunocytochemical staining. RESULTS: Quercetin at concentrations ranging from 40 mumol/L to 100 mumol/L significantly inhibited the proliferation of MGC-803 cells in a dose- and time-dependent manner (P<0.01). TUNEL assay indicated that the number of apoptotic cells in quercetin-treated group was greater than that in the control group (P<0.01). Expression of P53 and C-myc protein decreased following quercetin induction in a dose-dependent manner, whereas P16 expression increased significantly compared with that of the control group (P<0.01). CONCLUSION: Quercetin can inhibit the growth and induce apoptosis of MGC-803 cells in a dose- and time-dependent manner. Its mechanisms may be relevant to the down-regulation of P53 and C-myc protein expression as well as up-regulation of P16 expression.