Apigenin Enhanced Radiation-Induced Apoptosis/Necrosis by Sensitization of LNCaP Prostate Cancer Cells to 6 MV Photon Beams

Document Type : Original Article


1 Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Haematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Radiology and Nuclear Medicine, School of Allied Medical Sciences Kermanshah University of Medical Sciences, Kermanshah, Iran


Whereas prostate cancer (PrCa) may be unresponsive or moderately responsive to radiation therapy (RT)- most common modality for treatment of PrCa- patients must receive a high dose of RT In order to achieve appropriate tumour control. However, this increase in radiation dose may lead to severe adverse effects in normal tissues. Sensitization of PrCa to radiation provides an alternate approach to improve the therapeutic efficacy of RT. This study aims to assess the radiosensitisation effect of apigenin (Api) on a prostate cancer cell line (LNCaP).
Materials and Methods
In this experimental study, LNCaP cells were treated with 0-80 µM Api to investigate its effect on LNCaP cell viability and determine its half-maximal inhibitory concentration (IC50). Next, the cells were divided into four groups: i. Control, ii. Cells treated with the IC50 concentration of Api, iii. Cells treated with 2 Gy ionizing radiation (IR), and cells co-treated with Api and IR. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time polymerase chain reaction (PCR), and an Annexin V-FITC/PI assay were performed to assess cell survival, Bax and Bcl-2 expressions, and presence of apoptosis and necrosis.
Api inhibited cell survival in a dose-dependent, but not time-dependent manner. Cells treated with Api had increased amounts of early apoptosis, late apoptosis, and secondary necrosis compared to the control group. This group also had decreased Bcl-2 gene expression and up-regulated Bax gene expression. Co-treatment with Api and IR significantly inhibited cell survival, and increased early apoptosis, late apoptosis and secondary necrosis compared to the other groups. There was a significant decrease in Bcl-2 gene expression along with up-regulation of Bax gene expression, and Bax/Bcl-2 ratio changes that favoured apoptosis.
Api inhibited PrCa cell survival and induced apoptosis as a single agent. In addition, Api significantly sensitized the LNCaP cells to IR and enhanced radiation-induced apoptosis.