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 degrees 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 mu g/mL) for 24, 48, and 72 hours at 37 degrees 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 mu g/mL) and A172 (IC(5)0, 51.9 +/- 6.7 mu g/mL); at the 48-hour incubation time: 4T1 (IC50, 30.6 +/- 2.6 mu g/mL) and CT26 (IC50, 53.2 +/- 3.6 mu g/mL); and at the 72-hour incubation time: HT29 (IC50, 37.1 +/- 1.4 mu g/mL) and 4T1 (IC50, 62.2 +/- 4.8 mu g/mL). Both human and mouse BMDSCs showed the highest resistance at the 24-hour incubation time (IC(50)s, 254.7 +/- 21 and 204.4 +/- 4.5 mu g/mL, respectively) and the highest sensitivity at the 72-hour incubation time (IC(50)s, 120.4 +/- 5 and 159.0 +/- 7.3 mu g/mL, respectively). The PBMCs of both human and mouse origin revealed very strong resistance to the studied concentrations of umbelliprenin (IC(50)s ranging from 713.5 +/- 499.1 to 6651 +/- 3670.7 mu g/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.