The modulation of radiation-induced cell death by genistein in K562 cells: Activation of thymidine kinase 1

Abstract

Ionizing radiation is one of the most effective tools in cancer therapy. In a previous study, we reported that protein tyrosine kinase (PTK) inhibitors modulate the radiation responses in the human chronic myelogenous leukemia (CML) cell line K562. The receptor tyrosine kinase inhibitor, genistein, delayed radiation-induced cell death, while non-recepter tyrosine kinase inhibitor, herbimycin A (HMA) enhances radiation-induced apoptosis. In this study, we focused on the modulation of radiation-induced cell death by genistein and performed PCR-select suppression subtractive hybridization (SSH) to understand its molecular mechanism. We identified human thymidine kinase 1 (TK1), which is cell cycle regulatory gene and confirmed expression of TK1 mRNA by Northern blot analysis. Expression of TK1 mRNA and TK 1 enzymatic activity were parallel in their increase and decrease. TK1 is involved in G1-S phase transition of cell cycle progression. In cell cycle analysis, we showed that radiation induced G2 arrest in K562 cells but it was not able to sustain. However, the addition of genistein to irradiated cells sustained a prolonged G2 arrest up to 120 h. In addition, the expression of cell cycle-related proteins, cyclin A and cyclin B1, provided the evidences of G1/S progression and G2-arrest, and their relationship with TK1 in cells treated with radiation and genistein. These results suggest that the activation of TK1 may be critical to modulate the radiation-induced cell death and cell cycle progression in irradiated K562 cells.

FLT-PET Imaging of Radiation Responses in Murine Tumors

“…According to our cell cycle studies, G2/M arrest might be involved in decreasing FLT uptake after irradiation. This is consistent with previous findings on radiation-induced G2/M arrest [35]. Although the overall fraction of cells in the S-phase decreased less than as expected, one can still infer that the TK1 activity was suppressed when the cell cycle was arrested or with a prolonged cycling time post irradiation, thus leading to reduced uptake of FLT.…”

Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis

“…Hence, the MetS environment may suppress the antiapoptosis ability of Aurka, and APN treatment may significantly recover its expression. Thymidine kinase 1 (TK1) is a cytoplasmic enzyme functioning in phosphorylation and DNA synthesis and acts in renoprotection against apoptosis [28]. In this study, TK1 might play important roles in the repair of injured proximal tubular cells by GOx, and APN treatment may improve this ability, leading to renoprotection against crystal formation.…”

Gene expression pattern in apoptotic QGY-7703 cells induced by homoharringtonine

“…Thymidine kinase 1 (TK1) is a cell cycle regulatory gene involved in the G 1 -S phase transition during cell cycle progression. The activation of TK1 may be critical to modulate radiation-induced cell death and cell cycle progression in irradiated K562 cells [35] . GADD34 is also known PPP1R15A, which is protein phosphatase 1, regulatory (inhibitor) subunit 15A.…”