Umbelliprenin is potentially toxic against the HT29,CT26,MCF-7,4T1,A172,and Gl26 cell lines,potentially harmful against bone marrow-derived stem cells,and non-toxic against peripheral blood mononuclear cells

Background: Resistance to chemotherapy is a growing concern,thus natural anticancer agents are drawing the attention of many scientists and clinicians.One natural anticancer agent,umbelliprenin,is a coumarin produced by many species of Ferula.Objectives: We aimed to examine the inhibitory effect of umbelliprenin on human and mouse bone marrow-derived stem cells (BMDSCs),peripheral blood mononuclear cells (PBMCs),and different cancer cell lines.Materials and Methods: In this in vitro experimental study,the HT29,CT26,MCF-7,4T1,A172,and GL26 cancer cells and human and mouse BMDSCs and PBMCs were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS),incubated at 37°C for 24 hours in a 5% CO2 atmosphere,and then were treated with different concentrations of umbelliprenin dissolved in dimethyl sulfoxide (DMSO) (3,6,12,25,50,100,and 200 μg/mL) for 24,48,and 72 hours at 37°C.Each experiment was performed in triplicate.Finally,the cell survival rate was assessed byMTT assay.The IC50 values were calculated based on the log values using GraphPad Prism version 5 software for windows (La Jolla CA,USA) and were expressed as mean±SEM.Results: Umbelliprenin inhibited the cancer cells in a concentration-dependent (P <0.05) but not time-dependent manner (P >0.05).The most sensitive and resistant cell lines at the 24-hour incubation time were 4T1 (IC50,30.9±3.1 μg/mL) and A172 (IC50,51.9 ± 6.7 μg/mL);at the 48-hour incubation time: 4T1 (IC50,30.6 ± 2.6 μg/mL) and CT26 (IC50,53.2 ± 3.6 μg/mL);and at the 72-hour incubation time: HT29 (IC50,37.1±1.4 μg/mL) and 4T1 (IC50,62.2±4.8 μg/mL).Both human and mouse BMDSCs showed the highest resistance at the 24-hour incubation time (IC50s,254.7 ± 21 and 204.4 ± 4.5 μg/mL,respectively) and the highest sensitivity at the 72-hour incubation time (IC50s,120.4±5 and 159.0±7.3μg/mL,respectively).The PBMCs of both human and mouse origin revealed very strong resistance to the studied concentrations of umbelliprenin (IC50s ranging from 713.5±499.1 to 6651±3670.7 μg/mL).Conclusions: Our findings indicate that umbelliprenin exhibits concentration-dependent inhibitory effects on various cell types;it is potentially toxic against the HT29,CT26,MCF-7,4T1,A172,and GL26 cell lines,potentially harmful against BMDSCs,and non-toxic against PBMCs.Therefore,if our results are approved in the future,umbelliprenin can be an appropriate candidate for developing treatments against different cancers.© 2016,Iranian Red Crescent Medical Journal.

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