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12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury. 2017

Yaojie Liang, and Hongwei Zhou, and Yibing Yao, and Ailing Deng, and Zhihong Wang, and Boning Gao, and Minhang Zhou, and Yu Cui, and Lili Wang, and Lei Zhou, and Bianhong Wang, and Li Wang, and Anqi Liu, and Lanlan Qiu, and Kun Qian, and Yejian Lu, and Wanping Deng, and Xi Zheng, and Zhengtao Han, and Yonghui Li, and Junzhong Sun
Department of Geriatric Oncology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.

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.

UI MeSH Term Description Entries
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011832 Radiation Injuries Harmful effects of non-experimental exposure to ionizing or non-ionizing radiation in VERTEBRATES. Radiation Sickness,Radiation Syndrome,Injuries, Radiation,Injury, Radiation,Radiation Injury,Radiation Sicknesses,Radiation Syndromes,Sickness, Radiation,Sicknesses, Radiation,Syndrome, Radiation,Syndromes, Radiation
D011837 Radiation-Protective Agents Drugs used to protect against ionizing radiation. They are usually of interest for use in radiation therapy but have been considered for other purposes, e.g. military. Radiation Protectant,Radiation Protective Agent,Radiation-Protective Agent,Radiation-Protective Drug,Radioprotective Agent,Radioprotective Agents,Radioprotective Drug,Agents, Radiation-Protective,Radiation Protectants,Radiation Protective Agents,Radiation-Protective Drugs,Radiation-Protective Effect,Radiation-Protective Effects,Radioprotective Drugs,Agent, Radiation Protective,Agent, Radiation-Protective,Agent, Radioprotective,Agents, Radiation Protective,Agents, Radioprotective,Drug, Radiation-Protective,Drug, Radioprotective,Drugs, Radiation-Protective,Drugs, Radioprotective,Effect, Radiation-Protective,Effects, Radiation-Protective,Protectant, Radiation,Protectants, Radiation,Protective Agent, Radiation,Protective Agents, Radiation,Radiation Protective Drug,Radiation Protective Drugs,Radiation Protective Effect,Radiation Protective Effects
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D005260 Female Females

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