The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

Medicinal plants with hepatoprotective activity in Iranian folk medicine

There are a number of medicinal combinations in the Iranian traditional medicine which are commonly used as tonic for liver.In this review,we have introduced some medicinal plants that are used mainly for the treatment of liver disorders in Iranian folk medicine,with focus on their hepatoprotective effects particularly against CCI_4 agent.In this study,online databases including Web of Science.PubMed.Scopus,and Science Direct were searched for papers published from January 1970 to December 2013.Search terms consisted of medicinal plants,traditional medicine,folk medicine,hepatoprotective.Iran,liver,therapeutic uses,compounds,antioxidant.CCI_4.anti-inflammatory,and antihepatotoxic,hepatitis,alone or in combination.Allium hirtifolium Boiss..Apium graveolens L..Cynara scolyinus.Berberis vulgaris L..,Calendula officinalis,Nigella sativa L..Taraxacum officinale.Tragopogon porrifolius.Prangos ferulacea L..Allium sativum,Marribium vulgare,Ammi majus L..Citrullus lanatus Thunb.Agrimonia eupatoria L.and Primus armeniaca L.are some of the medicinal plants that have been used for the treatment of liver disorders in Iranian folk medicine.Out of several leads obtained from plants containing potential hepatoprotective agents,silymarin,P-sitosterol,betalain,neoandrographolide.phyllanthin.andrographolide.curcumin.picroside.hypophyllanlhin.kutkoside,and glycyrrhizin have been demonstrated to have potent hepatoprotective properties.Despite encouraging data on possibility of new discoveries in the near future,the evidence on treating viral hepatitis or other chronic liver diseases by herbal medications is not adequate.