Iodine-131 induces cell death by downregulation of antiapoptotic genes in MCF-7 human adenocarcinoma cells

Abstract

Aims: Radioiodine (131I) is the most common radionuclide which possesses favorable nuclear characteristics for targeted therapy in cancer management. There are several therapeutic radiopharmaceuticals labeled with 131I used in clinics, but the basic mechanism describing the cause of induced cell death is limited in literature. Hence, the aim of the present study is to find a plausible mechanism of cellular toxicity and involvement of antiapoptotic gene in induction of cell death due to 131I. Materials and Methods: The effect of 131I on cell death was studied by incubating MCF-7 cell line with different amount of 131I radioactivity for 6 h followed by washing and extended the incubation for 48 h. Cells were harvested and cell viability was assessed by lactate dehydrogenase (LDH) release and trypan blue dye uptake. Apoptosis study was carried out with enzyme-linked immunosorbent assay method. Reverse transcriptase polymerase chain reaction was carried out to find expression of antiapoptotic genes, viz., BCL-2 and BCLXL. Results: It was found that release of LDH was Dose and time dependent, and 35% cell death was estimated by trypan blue with 37 MBq of 131I radioactivity at 48 h of incubation. Enrichment factor of apoptotic DNA was 3.2 with 37 MBq of 131I at 48 h. Densitometric analysis of BCL-2 and BCLXLshowed that there is downregulation of genes expression, which confirmed apoptotic cell death. Conclusions: 131I induces apoptosis in MCF-7 cell line by the downregulation of antiapoptotic gene BCL-2 and BCLXLwhen exposed for longer time periods.

Keywords

• Apoptosis
• BCL-2
• BCLXL
• lactate dehydrogenase
• radioiodine