Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo

Lin, Chenghe; Yu, Yan; Zhao, Hong-guan; Yang, Aimin; Yan, Hong; Cui, Yali

doi:10.1016/j.radonc.2011.10.023

« BackRadiotherapy & Oncology

Article in Press

Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo

Chenghe Lin
- Department of Nuclear Medicine, Jilin University, Changchun, China
- Corresponding authors. Addresses: Department of Nuclear Medicine, The First Hospital, Jilin University, 71 Xinmin Road, Changchun, China (C. Lin), Department of Nuclear Medicine, Cancer Hospital, Harbin Medical University, 194 XueFu Road, Harbin 150081, China (Y. Cui).
- These authors contribute equally to the project.
Yan Yu
- Department of Public Health, Xi’an Jiaotong University School of Medicine, Xi’an, China
- These authors contribute equally to the project.
Hong-guan Zhao
- Department of Nuclear Medicine, Jilin University, Changchun, China
Aimin Yang
- Department of Public Health, Xi’an Jiaotong University School of Medicine, Xi’an, China
Hong Yan
- Department of Public Health, Xi’an Jiaotong University School of Medicine, Xi’an, China
Yali Cui
- Department of Nuclear Medicine, Harbin Medical University, Harbin, China
- Corresponding authors. Addresses: Department of Nuclear Medicine, The First Hospital, Jilin University, 71 Xinmin Road, Changchun, China (C. Lin), Department of Nuclear Medicine, Cancer Hospital, Harbin Medical University, 194 XueFu Road, Harbin 150081, China (Y. Cui).

Received 26 May 2011; received in revised form 22 September 2011; accepted 29 October 2011. published online 28 November 2011.
Corrected Proof

Abstract

Purpose

Quercetin (3, 3,′ 4′, 5, 7 – five-flavonoids) is one of the main components of flavonoids, with multifunctions on immune function, anti-oxidation, anti-viral, anti-inflammatory, and cardiovascular protection. We hypothesize that a combination of quercetin with radiation would increase tumor radiosensitivity. To test this hypothesis, we conducted in vitro and in vivo studies.

Methods and materials

The in vitro radio-sensitization activity of quercetin was tested in DLD1, HeLa and MCF-7 tumor cell lines by colony formation assays. The in vivo activity was assessed in the DLD-1 human colorectal cancer xenograft model in nude mice. Mechanistic studies were conducted in several cell lines using Western blot analysis and immunofluorescence microscopy.

Results

We found that quercetin can significantly increase tumor radiosensitivity both in vitro and in vivo. The in vitro Sensitizing Enhancement Ratios in DLD1, HeLa and MCF-7 cells were 1.87, 1.65, and 1.74, respectively. The mean doubling time of tumor xenografts was significantly increased in irradiated mice treated with quercetin. At the cellular level, exposure to quercetin resulted in prolonged DNA repair. The mechanistic studies demonstrated that quercetin induced radio-sensitization is through inhibiting the ATM kinase, one of the critical DNA damage response proteins.

Conclusion

We demonstrate both in vitro and in vivo evidence that combination of quercetin with radiotherapy can enhance tumor radiosensitivity by targeting the ATM-mediated pathway in response to radiation.

Keywords: Quercetin, Radiotherapy, ATM