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Research On Anti-tumor Activity Of Strong Alkaline Alkaloids From Crinum

Posted on:2015-01-25Degree:MasterType:Thesis
Country:ChinaCandidate:L GuoFull Text:PDF
GTID:2404330491960191Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
It is reported that Crinum has the effect of anti-tumor,but its composition and anti-tumor mechanism is not clear.In this paper,we study on the active groups of Crinum alkaloids:strong alkaline of Crinum alkaloids(WSLQJ)and explore its anti-tumor mechanisms and pathways.MTT test showed that:WSLQJ has significantly inhibited on human gastric cancer cell SGC-7901,hepatoma cells HepG-2,breast cancer cells MCF-7 and hepatoma cells SMMC-7721.They are in a dose-dependent manner with IC5o=16.555?g·mL-1,16.373?g mL-1,6.219?g·mL-1,25.842?g·mL-1.WSLQJ has a particularly prominent of inhibitory effect on MCF-7 cells.Cell morphology experiments showed that:with increasing dose of WSLQJ,cell apoptosis bodies appeared and gradually increased.Apoptosis rate measurement showed that:apoptosis rate rise with the increasing dose and it has a dose-dependent manner.Administration concentrations were 3?g·mL-1,6?g·mL-1,12?g·mL-1.The above results show that WSLQJ can inhibit the growth of MCF-7 cells,and induce apoptosis of MCF-7 cells.This provides a basis for further research of mechanism.Intracellular Ca2+ concentration test showed:Ca2+concentration rises with an increasing dose and showing a dose-dependent manner.Cytoplasmic expression of Cyt-C detection experiments showed that:WSLQJ can promote Cyt-C release from mitochondria into the cytosol.The results of intracellular caspase-3 activity assay showed that:WSLQJ can increase the activity of caspase-3 and showing a positive correlation.Administration concentrations were 3?g·mL-1,6?g·mL-1,12?g·mL-1.The above shows that WSLQJ induced apoptosis of breast cancer MCF-7 in mitochondrial pathway:WSLQJ promote Ca2+release from the endoplasmic reticulum,and mitochondria Ca2+ Overload and format permeability hole,mitochondria begin to swell,then mitochondrial outer membrane danaged and then Cyt-C release into the cytoplasm.Cyt-C binding Apaf-1,caspase-9 precursor,ATP/dATP formation of apoptotic bodies,and then convene and activate caspase-3,triggering caspase cascade,leading to apoptosis.In summary WSLQJ can induce tumor cell apoptosis through mitochondrial pathway.
Keywords/Search Tags:Crinum strong alkaline alkaloids, apoptosis, MCF-7 cell, mitochondrial pathway
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