REGULAR ARTICLES

Cell Research (2004); 14(4):295-302

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

Min Ho JEONG¹, Young Hee JIN¹, Eun Young KANG¹, Wol Soon JO¹, Hwan Tae PARK¹, Jae Dong LEE², Yeo Jin YOO¹, Soo Jin JEONG^1,3,

¹Research Supporting Center for Medical Science (BK21 program), Dong-A University College of Medicine, Busan, Korea.
²Department of Microbiology, Pusan National University, Busan, Korea.
³Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institutes, National Institute of Health, Bethesda, MD 20892, USA.

Received, Jan 21 , 2004    Revised, May 10, 2004    Accepted, May 25, 200

Correspondence: Soo Jin JEONG 01-301-496-0986 (phone) 01-301-496-4951 (fax) jeongs@mail.nih.gov

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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.

Keywords: K562, radiation, cell death, genistein, thymidine kinase 1, cell cycle.