The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

作者：Skonieczna Magdalena; Cieslar Pobuda Artur; Saenko Yuriy; Foksinski Marek; Olinski Ryszard; Rzeszowska Wolny Joanna; Wiechec Emilia^*

来源：Medicinal Chemistry, 2017, 13(5): 477-483.

DOI：10.2174/1573406413666170421102353

• 4,4' -diisothiocyanostilbene-2,2' -disulfonic acid (DIDS)
• voltage-dependent anion channel (VDAC)
• reactive oxygen species (ROS)
• ionizing radiation
• cell death
• DNA strand breaks

Background: The voltage-dependent anion channels (VDAC) play an essential role in the cross talk between mitochondria and the rest of the cell. Their implication in cell life and cell death has been studied extensively in recent years. In this work we studied the impact of mitochondrial membrane (VDACs) on cell survival and response to X-ionizing radiation (IR) of human lymphoblastoid K562 cells.
Methods: The inhibition of VDACs was achieved by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibitor and in vitro experiments including clonogenity assay, UV-visible spectrophotometry, comet assay and FACS analysis were implemented.
Results: Inhibition of VDAC led to augmentation of IR-induced apoptosis and ROS production. Additionally, DIDS affected repair of IR-induced DNA strand breaks and was in line with both induction of apoptosis and caspase activity. The IR-induced NO production was potently reduced by inhibition of VDAC.
Conclusion: Our results suggest that VDAC control cellular response to ionizing radiation through modulation of the ROS-and NO-dependent signaling pathways. Inhibition of VDAC with DIDS induced apoptosis in irradiated K562 lymphoblastoid cells points at DIDS, as a promising agent to enhance the effectiveness of radiotherapy.

• 出版日期2017