Radiosensitization of human glioma cells by tamoxifen is associated with the inhibition of PKC-ι activity in vitro

Abstract

Abstract. The present study aimed to investigate the radiosensitizing effects of tamoxifen (TAM), a non-steroidal anti-estrogen drug, in human glioma A172 and U251 cells in vitro. A colony-forming assay revealed that TAM enhances radiosensitivity in A172 and U251 cells. Treatment with TAM also increased the percentage of apoptotic cells subsequent to ionizing radiation, and increased the expression of apoptotic markers, including cleaved caspase-3 and poly(ADP-ribose) polymerase. Ionizing radiation induced G2/M phase arrest, which was alleviated within 24 h when the radiation-induced DNA damage was repaired. However, flow cytometry analysis revealed that TAM treatment delayed the recovery of cell cycle progression. Additional examination demonstrated that TAM-mediated protein kinase C-ι (PKC-ι) inhibition may lead to the activation of pro-apoptotic B-cell lymphoma 2-associated death promoter, and the dephosphorylation of cyclin-dependent kinase 7, resulting in increased cell apoptosis and sustained G2/M phase arrest following exposure to radiation. The present data indicate that the radiosensitizing effects of TAM on glioma cells are partly due to the inhibition of PKC-ι activity in vitro.

Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

“…Newton and colleagues [ 65 ] observed an enhanced apoptotic cell death in MCF-7 cells which were treated by a combination of irradiation and ZM182780, a pure anti-estrogen, or tamoxifen. In a more recent study, tamoxifen enhanced the radiosensitivity of human glioma cells by inducing cell apoptosis and sustaining G2/M arrest [ 66 ]. Moreover, fulvestrant, another pure anti-estrogen drug, revealed a positive effect on radiosensitization of ER-positive breast cancer cells by inducing cell cycle arrest and inhibiting proteins involved in DSB repair [ 67 ].…”

Rationalizing Optimal Timing for Adjuvant Hormone Therapy for Patients with Breast Cancer: Impact on Limited Resource Countries

“…It increases the number of apoptotic cells which are more radiosensitive than other phases likely due to the increased number of targets. Thus, the final outcome is a positive balance in favor of Tamoxifen concurrently administered with radiotherapy, which is likely to act as a radio-sensitizer [22].…”

“…Several clinical and clinicopathological studies indicated: cytoreductive surgery for testicular tumors, enhanced tumor progression [20], and post-surgical accelerated growth of metastasis in non-small cell lung cancer [22]. Improved survival and relapse following Laparoscopic cholecystectomy compared to open cholecystectomy Table 3.…”

Measuring the lactate-to-creatine ratio via 1H NMR spectroscopy can be used to noninvasively evaluate apoptosis in glioma cells after X-ray irradiation

“…Previous studies demonstrated that DNA damage could induce tumor cell apoptosis, and that this is associated with protein kinase C (PKC) activation [ 3 – 7 ] . Furthermore, recent advances in the study of tumors show that PKC iota (PKC-ι) expression is highly upregulated in tumor cells [ 4 , 8 ]. Notably, Yang et al suggested that the in vitro radiosensitizing effects of tamoxifen on glioma cells were partly caused by the inhibition of PKC-ι activity [ 4 ].…”

“…Furthermore, recent advances in the study of tumors show that PKC iota (PKC-ι) expression is highly upregulated in tumor cells [ 4 , 8 ]. Notably, Yang et al suggested that the in vitro radiosensitizing effects of tamoxifen on glioma cells were partly caused by the inhibition of PKC-ι activity [ 4 ]. We also recently demonstrated that X-ray irradiation could lead to inhibition of PKC-ι activity, and that this correlated with the radiosensitivity of the cells [ 9 ].…”