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

Abstract EN

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 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 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, 30.93.1 g/m L) and A172 (IC50, 51.9 6.7 g/m L); at the 48-hour incubation time: 4T1 (IC50, 30.6 2.6 g/mL) and CT26 (IC50, 53.2 3.6 g/mL); and at the 72-hour incubation time: HT29 (IC50, 37.11.4 g/mL) and 4T1 (IC50, 62.24.8 g/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 g/mL, respectively) and the highest sensitivity at the 72-hour incubation time (IC50s, 120.45 and 159.07.3g/mL, respectively).

The PBMCs of both human and mouse origin revealed very strong resistance to the studied concentrations of umbelliprenin (IC50s ranging from 713.5499.1 to 66513670.7 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.