Emodin attenuates radioresistance induced by hypoxia in HepG2 cells via the enhancement of PARP1 cleavage and inhibition of JMJD2B

Hwang,Sang  Youn; Heo,Kyu; Kim,Joon  Seok; Im,Jung  Woo; Lee,Sun  Mi; Cho,Mong; Kang,Dae  Hwan; Heo,Jeong; Lee,Jun  Woo; Choi,Cheol  Won; Yang,Kwangmo

doi:10.3892/or.2015.3744

Emodin attenuates radioresistance induced by hypoxia in HepG2 cells via the enhancement of PARP1 cleavage and inhibition of JMJD2B

Authors:
- Sang Youn Hwang
- Kyu Heo
- Joon Seok Kim
- Jung Woo Im
- Sun Mi Lee
- Mong Cho
- Dae Hwan Kang
- Jeong Heo
- Jun Woo Lee
- Cheol Won Choi
- Kwangmo Yang
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Affiliations: Department of Internal Medicine, Dongnam Institute of Radiological and Medical Sciences, Busan, Republic of Korea, Department of Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Republic of Korea, Department of Internal Medicine, Pusan National University College of Medicine, Busan, Republic of Korea, Department of Radiology, Pusan National University College of Medicine, Busan, Republic of Korea, Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Republic of Korea
Published online on: January 21, 2015 https://doi.org/10.3892/or.2015.3744
Pages: 1691-1698

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Abstract

Radioresistance in the tumor and radiotoxicity in the non‑tumorous liver significantly restrict efficient radiotherapy of hepatocellular carcinoma (HCC). It is therefore important to study the radioresistance mechanism and development of radiosensitization to optimize the effect of irradiation on cancer cells. Emodin (1, 3, 8‑trihydroxy‑6‑methylanthraquinone) is a plant‑derived polyphenol, possessing anticancer properties. It is known to act as a radiosensitizer in human HCC cell lines. The aim of this study was to evaluate the role of emodin in radioresistance of human HCC cell lines as well as the underlying radiosensitization mechanism. The human HCC cell line (HepG2) was used in this study. Four different treatment groups, i.e., no treatment (control), irradiation (10 Gy, one fraction), emodin (10 µM), and a combination of irradiation and emodin (10 Gy +10 µM) were used for two environmental conditions: hypoxia (1% O2) and normoxia (20% O2). The cells were exposed to the respective treatments for 24 and 72 h. Following the treatment, the cell viability was determined by the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay, and the radiosensitization mechanism was evaluated by western blotting. The proliferation of HepG2 cells was significantly suppressed in the treatment groups under hypoxic and normoxic conditions in the following order: combination of irradiation and emodin > irradiation only > emodin only. The combination of irradiation and emodin induced apoptotic signaling activities such as cleavage of poly (ADP‑ribose) polymerase (PARP)‑1 as well as the downregulation of epigenetic signaling such as JMJD1A and JMJD2B. Emodin attenuated radioresistance in the HepG2 cells via upregulation of the apoptotic signals and downregulation of the proliferative signals. These results suggested that emodin is a potential candidate for the radiosensitization of HCC cells and can aid in identifying novel therapeutic strategies for HCC radiotherapy.

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