12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury
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Yaojie Liang1,*, Hongwei Zhou1,*, Yibing Yao1,*, Ailing Deng2, Zhihong Wang1, Boning Gao3, Minhang Zhou1, Yu Cui4, Lili Wang5, Lei Zhou5, Bianhong Wang6, Li Wang7, Anqi Liu8, Lanlan Qiu9, Kun Qian6, Yejian Lu5, Wanping Deng1, Xi Zheng1, Zhengtao Han10, Yonghui Li5 and Junzhong Sun1
1Department of Geriatric Oncology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China
2Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
3Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas, USA
4State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing, China
5Department of Hematology, Chinese PLA General Hospital, Beijing, China
6Department of Hematology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
7Department of Hematology, Laoshan Branch, No.401 Hospital of Chinese PLA, Qingdao, China
8Department of Critical Care Medicine, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
9Department of Hematology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
10Henan Tumor Research Institute, Zheng Zhou, China
*These authors have contributed equally to this work
Junzhong Sun, email: [email protected]
Yonghui Li, email: [email protected]
Zhengtao Han, email: [email protected]
Keywords: 12-O-tetradecanoylphorbol-13-acetate (TPA), intestinal crypt stem cells, radiation injury, IEC-6 cell and BALB/c mouse, radioprotection
Received: June 06, 2016 Accepted: March 22, 2017 Published: April 20, 2017
Radiation enteropathy is a common complication in cancer patients following radiation therapy. Thus, there is a need for agents that can protect the intestinal epithelium against radiation. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to induce differentiation and/or apoptosis in multiple cell lines and primary cells. In the current report, we studied the function of TPA in radiation induced enteropathy in cultured rat intestinal epithelial cell line IEC-6 after ionizing radiation (IR) and in mice after high dose total-body gamma-IR (TBI). In IEC-6 cells, there were reduced apoptosis and cell cycle arrest in TPA treated cells after IR. We detected a four-fold increase in crypt cell survival and a two-fold increase in animal survival post TBI in TPA treated mice. The beneficial effects of TPA were accompanied by upregulation of stem cells markers and higher level of proteins that are involved in PKC signaling pathway. In addition, TPA also decreased the TBI-augmented levels of the DNA damage indicators. The effects were only observed when TPA was given before irradiation. These results suggest that TPA has the ability to modulate intestinal crypt stem cells survival and this may represent a promising countermeasure against radiation induced enteropathy.
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