Study On Activity And Mechanism Of Anticancer Properties Of Mogrol And Its Derivatives

Cancer is becoming a major threat to human health,the research and development of cancer prevention and anti-cancer drugs has a long way to go.The natural compounds which come from plant have the advantages of easily drawn,cheap and less toxic side effects,etc.Therefore,researchers have focused on the traditional Chinese medicine and its active ingredients.Momordica grosvenori Swingle is the first batch of medicine and food traditional Chinese medicine,that approved by ministry of health and State Administration of Traditional Chinese Medicine.In the public,people make use of Mangosteen tea to prevent and treat nasopharyngeal cancer,laryngeal cancer,lung cancer and other cancers.And the modern pharmacological experiments also confirmed that Mogroside with good cancer prevention and anti-cancer ability,having the potential to become a new cancer chemopreventive and treatments drug.Therefore it urgently need to systematically study the mechanisms of its cancer prevention and anti-cancer ability,however the metabolic studies of mogrosides suggests that its pharmacological activity may be mainly come from Aglycone(Mogrol).So the anti-cancer ability of mogrol was be evaluated in this paper,after exactly sure it has cancer prevention and anti-cancer activity,we used the experience and computer drug design methods for structural modification of Mogrol,to synthetic series of Mogrol derivative,then we screened out the more efficiently anti-cancer compounds and take preliminary mechanism study on these compounds and mogrol.Result of this paper provided a reliable theoretical basis for cancer prevention and anti-cancer aspects of application development,and further expanded the medicinal value of Momordica grosvenori Swingle.The main results of this research include the following aspects:1.Inhibitory effects of mogrol on the proliferation of various tumor cells.Cell proliferation was measured by colorimetric methyl thiazolyl tetrazolium(MTT)assay on DU 145,HepG2,A549,CNE1 and CNE2 tumor cells,the results showed that mogrol could significantly inhibit the proliferation of these tumor cells,the IC50 values were 90.28?M,90.31?M,89.51?M,81.48?M,84.04?M,and the inhibitory effect of CNE1 cells were the most significant.So we choose CNE1 cells as the research object of follow-up.2.Influence of mogrol on the colony formation of CNE1 cell.Through colonyforming assay on CNE1 cells,we found different concentrations(50?M,100?M,200?M)of mogrol lead different cloning efficiency(72.45± 13.67%,18.45±7.51%,12.64±8.66%).The result stated that mogrol could inhibit the clones formation of CNE1 cells and further validated the mogrol could inhibit the proliferation of CNE1 cells.3.Inhibitory effects of mogrol on the migration of CNE1 cells.Through the cell healing assay,we found that under the action of mogrol and with the increase of concentration and time,the migrate ability of CNE1 cell was gradually weakened,or even unable to migrate.The result stated that mogrol could effectively inhibit the migration of CNE1 cells in a time and concentration-dependent manner.4.The anti-cancer activity screening of mogrol derivatives.MTT assays were used to evaluate the anti-cancer activity of Mogrol derivatives on five tumor cells,the results show that G1,G2,G3 have better anti-cancer activity,and the activity was stronger than the mogrol.The IC50 values of CNE1 cells were 40.93?M,40.21?M and 36.61?M.By analyzing their chemical structure,we found that compared with mogrol they lack a hydroxyl group,which may be the reason that they have a stronger anti-tumor activity.5.Influence of mogrol and G2 on the apoptosis of CNE1 cell.By the AnnexinV/PI double staining test,we found that after CNE1 cells were treated with different concentrations of mogrol and G2 for 24h,the cell apoptosis rate of CNE1 cells was increased with the rise of concentrations,and the apoptotic cells were mainly late apoptotic cells.The result illustrated that mogrol and G2 could induce CNE1 cells apoptosis in a concentration dependent manner,and mainly induce cells in the late apoptosis.6.Effects of mogrol and G2 on the mRNA expression levels of Caspase-3,Survivin,Bax and Bcl-2 genes in CNE1 cell.We apply real-time PCR technology to measure the mRNA expression levels of Caspase-3,Survivin,Bax and Bcl-2 genes in CNE1 cell.The result showed that mogrol and G2 could upregulated the expression of Caspase-3,Bax and other pro-apoptotic genes and down the expression of Survivin Bcl-2 and other anti-apoptotic genes.Therefore,mogrol and G2 probably by promoting the expression of Caspase-3 Bax and other pro-apoptotic genes and inhibit the expression of Survivin Bcl-2 and other anti-apoptotic genes,inducing the apoptosis of tumor cells,and result in anti-tumor activity.7.Influence of mogrol on the inhibition of lung transplanted tumor in mice.Mogrol was fed to Lewis tumor-burdened mice to study the influence of mogrol on the inhibition of transplanted tumor in mice and observe the influence of mogrol on the immune organ in mice.The results showed that the tumor weight of mogrol high-dose group and low dose group were slightly larger than the model group,the inhibition rate was 11.08%and 7.11%respectively,it illustrated that the influence of mogrol on the inhibition of transplanted tumor was not obvious,However,the high doses(200mg/kg)of mogrol could significantly increase the spleen index and thymus index in Lewis tumor-bearing mice,to improve the body's immunity.