title: 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: 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 ofFerula.
  
  
  OBJECTIVE
  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.
  
  
  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% CO2atmosphere, 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 by MTT assay. The IC50values 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 ± 7.3 µg/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.
authors.affiliation: Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Rashidi
authors.affiliation: Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Ziai
authors.affiliation: Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Taraneh
authors.initials: T
authors.lastname: Moini Zanjani
authors.affiliation: Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Ahad
authors.initials: A
authors.lastname: Khalilnezhad
authors.affiliation: Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Jamshidi
authors.affiliation: Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Davar
authors.initials: D
authors.lastname: Amani
keywords: Inhibition; Natural Product; Neoplastic Cell; Umbelliprenin