Petrović Sandra, Vasić Vesna, Mitrović Tatjana, Lazović Saša, Leskovac Andreja
Vinča Institute of Nuclear Sciences, Belgrade.
University of Belgrade, Institute for Development of Water Resources "Jaroslav Černi", Belgrade.
Arh Hig Rada Toksikol. 2017 Mar 1;68(1):1-8. doi: 10.1515/aiht-2017-68-2897.
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.
据报道,十一烷基灵菌红素色素(UPP)对多种类型的肿瘤具有细胞毒性活性。然而,其在改变细胞对电离辐射的反应方面的功效仍然未知。在本研究中,对UPP的辐射调节作用进行了研究。通过使用两种治疗方案,即UPP预照射治疗和UPP后照射治疗,用UPP和电离辐射处理人外周血培养物,在体外评估UPP的作用。通过评估UPP对辐射诱导的微核形成、细胞增殖和凋亡诱导的影响来研究UPP的活性。通过测量过氧化氢酶活性和丙二醛水平来检查UPP的氧化还原调节作用,作为氧化应激的指标。结果表明,UPP对细胞对电离辐射的反应的影响取决于其浓度和给药时间。在低浓度下,UPP在γ射线照射的人淋巴细胞中表现出辐射防护作用,而在较高浓度下,它作为放射增敏剂,根据治疗方案增强有丝分裂灾难或凋亡。UPP改变了细胞中的氧化还原过程,特别是在γ射线照射之前使用时。我们的数据强调了进一步研究UPP通过抑制导致治疗抗性的途径使肿瘤细胞对放射治疗敏感的潜力重要性。