Authors: Kwang Seok Kim, Kyu Jin Choi and Sangwoo Bae

Kwang Seok Kim

Divisions of Radiation Effects; Korea Institute of Radiological and Medical Sciences; Seoul, South Korea

Kyu Jin Choi

Divisions of Radiation Effects; Korea Institute of Radiological and Medical Sciences; Seoul, South Korea

Sangwoo Bae

Corresponding author: swbae@kcch.re.kr
Divisions of Radiation Effects; Korea Institute of Radiological and Medical Sciences; Seoul, South Korea

Abstract:
Interferon-gamma (IFNγ) is a cytokine with roles in immune responses as well as in tumor control. Interferon is often used in cancer treatment together with other therapies. Here we report a novel approach to enhancement of cancer cell killing by combined treatment of IFNγ with ionizing radiation.

We found that IFNγ treatment alone in HeLa cells induced phosphorylation of Chk1 in a time- and dose-dependent manner, and resulted in cell arrest. Moreover IFNγ treatment was correlated with attenuation of Chk1 as the treatment shortened protein half-life of Chk1. As Chk1 is an essential cell cycle regulator for viability after DNA damage, attenuation of Chk1 by IFNγ pre-treatment in HeLa cells resulted in increased cell death following ionizing radiation about 2-folds than ionizing radiation treatment alone whereas IFNγ treatment alone had little effect on cell death.

X-linked inhibitor of apoptosis-associated factor 1 (XAF1), an IFN-induced gene, seems to partly regulate IFNγ-induced Chk1 destabilization and radiation sensitivity because transient depletion of XAF1 by siRNA prevented IFNγ-induced Chk1 attenuation and partly protected cells from IFNγ-enhanced radiation cell killing.

Therefore the results provide a novel rationale to combine IFNγ pretreatment and DNA-damaging anti-cancer drugs such as ionizing radiation to enhance cancer cell killing.

Received: February 16, 2012; Accepted: June 4, 2012; Published Online: July 24, 2012

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