12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury

Yaojie Liang, Hongwei Zhou, Yibing 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, Yejian Lu, Wanping Deng, Xi Zheng, Zhengtao Han, Yonghui LiJunzhong Sun

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)45566-45576
Number of pages11
JournalOncotarget
Volume8
Issue number28
DOIs
StatePublished - 2017

Fingerprint

Radiation Injuries
Tetradecanoylphorbol Acetate
Cell Survival
Stem Cells
Ionizing Radiation
Radiation
Apoptosis
Cell Line
Gamma Rays
Intestinal Mucosa
Cell Cycle Checkpoints
DNA Damage
Up-Regulation
Radiotherapy
Epithelial Cells

Keywords

  • 12-O-tetradecanoylphorbol-13-acetate (TPA)
  • IEC-6 cell and BALB/c mouse
  • Intestinal crypt stem cells
  • Radiation injury
  • Radioprotection

ASJC Scopus subject areas

  • Oncology

Cite this

12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury. / Liang, Yaojie; Zhou, Hongwei; Yao, Yibing; Deng, Ailing; Wang, Zhihong; Gao, Boning; Zhou, Minhang; Cui, Yu; Wang, Lili; Zhou, Lei; Wang, Bianhong; Wang, Li; Liu, Anqi; Qiu, Lanlan; Qian, Kun; Lu, Yejian; Deng, Wanping; Zheng, Xi; Han, Zhengtao; Li, Yonghui; Sun, Junzhong.

In: Oncotarget, Vol. 8, No. 28, 2017, p. 45566-45576.

Research output: Contribution to journalArticle

Liang, Y, Zhou, H, Yao, Y, Deng, A, Wang, Z, Gao, B, Zhou, M, Cui, Y, Wang, L, Zhou, L, Wang, B, Wang, L, Liu, A, Qiu, L, Qian, K, Lu, Y, Deng, W, Zheng, X, Han, Z, Li, Y & Sun, J 2017, '12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury', Oncotarget, vol. 8, no. 28, pp. 45566-45576. https://doi.org/10.18632/oncotarget.17269
Liang, Yaojie ; Zhou, Hongwei ; Yao, Yibing ; Deng, Ailing ; Wang, Zhihong ; Gao, Boning ; Zhou, Minhang ; Cui, Yu ; Wang, Lili ; Zhou, Lei ; Wang, Bianhong ; Wang, Li ; Liu, Anqi ; Qiu, Lanlan ; Qian, Kun ; Lu, Yejian ; Deng, Wanping ; Zheng, Xi ; Han, Zhengtao ; Li, Yonghui ; Sun, Junzhong. / 12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury. In: Oncotarget. 2017 ; Vol. 8, No. 28. pp. 45566-45576.
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AU - Liang, Yaojie

AU - Zhou, Hongwei

AU - Yao, Yibing

AU - Deng, Ailing

AU - Wang, Zhihong

AU - Gao, Boning

AU - Zhou, Minhang

AU - Cui, Yu

AU - Wang, Lili

AU - Zhou, Lei

AU - Wang, Bianhong

AU - Wang, Li

AU - Liu, Anqi

AU - Qiu, Lanlan

AU - Qian, Kun

AU - Lu, Yejian

AU - Deng, Wanping

AU - Zheng, Xi

AU - Han, Zhengtao

AU - Li, Yonghui

AU - Sun, Junzhong

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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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