title: The impact of concentration and administration time on the radiomodulating properties of undecylprodigiosin in vitro.
abstract: Undecylprodigiosin pigment (UPP) is reported to display cytotoxic activity towards various types of tumours. Nevertheless, its efficacy in modifying the cellular response to ionising radiation is still unknown. In this study, the radiomodulating effects of UPP were investigated. The effects of UPP were assessed in vitro by treating cultures of human peripheral blood with UPP and ionising radiation using two treatment regimens, the UPP pre-irradiation treatment and UPP post-irradiation treatment. The activity of UPP was investigated evaluating its effects on the radiation-induced micronuclei formation, cell proliferation, and induction of apoptosis. The redox modulating effects of UPP were examined measuring the catalase activity and the level of malondialdehyde, as a measure of oxidative stress. The results showed that UPP effects on cellular response to ionising radiation depend on its concentration and the timing of its administration. At low concentration, the UPP displayed radioprotective effects in γ-irradiated human lymphocytes while at higher concentrations, it acted as a radiosensitiser enhancing either mitotic catastrophe or apoptosis depending on the treatment regimen. The UPP modified redox processes in cells, particularly when it was employed prior to γ-irradiation. Our data highlight the importance of further research of the potential of UPP to sensitize tumour cells to radiation therapy by inhibiting pathways that lead to treatment resistance.
authors.affiliation: Vinča Institute of Nuclear Sciences, Belgrade.
authors.forename: Sandra
authors.initials: S
authors.lastname: Petrović
authors.affiliation: Vinča Institute of Nuclear Sciences, Belgrade.
authors.forename: Vesna
authors.initials: V
authors.lastname: Vasić
authors.affiliation: University of Belgrade, Institute for Development of Water Resources "Jaroslav Černi", Belgrade.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Mitrović
authors.affiliation: Institute of Physics Belgrade, Belgrade.
authors.forename: Saša
authors.initials: S
authors.lastname: Lazović
authors.affiliation: Vinča Institute of Nuclear Sciences, University of Belgrade, M. Petrovića Alasa 12-14, 11001 Belgrade.
authors.forename: Andreja
authors.initials: A
authors.lastname: Leskovac
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011353:Prodigiosin / Q000633:toxicity*; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*
chemical_list: D011353:Prodigiosin
keywords: apoptosis; mitotic catastrophe; oxidative stress; radiosensitisation; undecylprodigiosin