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 g/mL) for 24, 48, and 72 hours at 37°C. Each experiment was performed in triplicate.Finally, the cell survival rate was assessed by MTT 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 meanSEM.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 mg/mL) and A172 (IC50, 51.9±6.7 mg/mL); at the 48-hour incubation time: 4T1 (IC50, 30.6±2.6 mg/mL) and CT26 (IC50, 53.2±3.6 mg/mL); and at the 72-hour incubation time: HT29 (IC50, 37.1±1.4 mg/mL) and 4T1 (IC50, 62.2±4.8 mg/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 mg/mL, respectively) and the highest sensitivity at the 72-hour incubation time (IC50s, 120.4±5 and 159.0±7.3mg/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 66513670.7 mg/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.