Open Access12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury
Author(s) -
Yaojie Liang,
Hongwei Zhou,
Yuanrong Yao,
Ailing Deng,
Zhihong Wang,
Boning Gao,
MinHang Zhou,
Yu Cui,
Lili Wang,
Lei Zhou,
Bianhong Wang,
Li Wang,
Anqi Liu,
Lanlan Qiu,
Kun Qian,
Ye-Jian Lu,
Wanping Deng,
Xi Zheng,
Zhengtao Han,
Yonghui Li,
Jian Sun
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.17269
Subject(s) - beijing , medicine , 12 o tetradecanoylphorbol 13 acetate , hematology , china , acute radiation syndrome , oncology , stem cell , family medicine , biology , haematopoiesis , history , genetics , archaeology , protein kinase c , enzyme , biochemistry , phorbol ester
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.