ABSTRACT
OBJECTIVE: To explore the effects of luteolin on the proliferation and migration of the endothelial cells co-cultured with cancer cells and its molecular mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were primarily isolated and identified by the expression of VE-cadherin. Cancer-endothelial cell co-culture model was established using the Transwell system. The effects of luteolin at different concentrations (0 [Co-culture control], 20 and 50 μmol•L-1) on the proliferation and migration of HUVECs in the co-culture system were determined. A HUVECs control group removed of prostate cancer PC3 cells was also included. Human angiogenesis antibody array kit was used to assay the secretion levels of various protein factors in each group. RESULTS: VE-cadherin was expressed on all the cultured HUVECs. Increased proliferation ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P < 0.01). Treatment with 20 or 50 μmol•L-1 luteolin significantly inhibited the proliferation ability of the HUVECs in co-culture system (both P < 0.01). Increased migration ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P < 0.01). Treatment with 20 or 50 μmol• L-1 luteolin significantly inhibited the migration ability of the HUVECs in co-culture system (both P < 0.01). Secretion levels of multiple angiogenesis-related proteins in the cultural supernatant of co-culture system were significantly increased compared with those in HUVECs control group. Treatment with 20 μmol•L-1 luteolin significantly inhibited the secretion levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1(MCP-1) in the cultural supernatant of co-culture system (all P < 0.01). CONCLUSION: Luteolin may inhibit the proliferation and migration of endothelial cells via suppressing the secretions of IL-8, VEGF and MCP-1 in cancer-endothelial co-culture system.
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OBJECTIVE: To investigate the cytotoxic activities of chemical constituents in alcohol extract of the stem bark of Murraya exotica L. METHODS: The cytotoxicity against five cancer cell lines, U937, HL-60, K562, Bel7402 and Hela, were assayed by MTT and SRB METHODS. The constituents were isolated from Murraya exotica L. by routine chromatographic METHODS and the structures of the isolates were elucidated by NMR techniques. The antitumor effect was evaluated on cancer cells in vitro. RESULTS: When the cancer cells were exposed to the extract for more than 48 h, the survival rate decreased with the increase of the drug concentration. Four compounds were isolated and identified as isolariciresinol (I), dimethoxy isolariciresinol (II), 3-methoxyisolariciresinol (III), and 5'-methoxyisolariciresinol (IV). CONCLUSION: The active ingredients in Murraya exotica L. have antitumor activities, which may be compounds I and II.
ABSTRACT
OBJECTIVE: To study the in vitro metabolism and enzyme kinetics of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride in rat liver microsomes, and to identify the major cytochrome P450 isozymes involved in the metabolism of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride in rat liver microsomes. METHODS: By optimizing the incubation conditions of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride in rat liver microsomes, the enzyme kinetics in different enzyme sources was researched; the cytochrome P450 isozymes involved in metabolism of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride were preliminarily explored through in vitro inhibition experiments. RESULTS: Different enzyme source metabolism experiments showed that between phenobarbital(PB) and desamethasone(Dex) induction groups and blank control group there had significant differences, but between the BNF group and blank control group there had no significant difference; the inhibition experiments revealed that ketoconazole had strong inhibition effect on di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride metabolism. CONCLUSION: CYP3A plays a leading role in di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride metabolism, and CYP2C9 may be partly involved. CYP1A has no catalysis action on metabolism of di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride. The Results suggest that attention should be paid to the possibility of drug interactions when di-n-butyl-(4-chlorobenzohydroxamato) tin(IV) chloride is combined with the drugs metabolized by above-mentioned isozymes.