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The present study evaluated the protective effect of the natural compound flavonoids of Rosa roxburghii Tratt (FRT) against γ-radiation-induced apoptosis and inflammation in mouse thymus cells in vivo and in vitro. Thymus cells and mice were exposed to Co γ-ray at a dose of 6 Gy. The radiation treatment induced significant cell apoptosis and inflammation. Radiation increased the expressions of cleaved caspase 3/8-10, AIF, and PARP-1, and FRT could mitigate their activation and inhibit subsequent apoptosis in the thymus both in vitro or in vivo. Irradiation increased the mRNA expression of ICAM-1/VCAM-1, IL-1α/IL-6 and TNF-α/NF-κB. Our results also indicated that FRT alleviated gene expression of some inflammatory factors such as ICAM-1/VCAM-1, TNF-α/NF-κB, but not IL-1α/IL-6. Irradiation increased the protein expression levels of ICAM-1/VCAM-1, IL-1α/IL-6 and TNF-α/NF-Κb, and our results also indicated that FRT alleviated protein level expression of certain inflammatory factors such as ICAM-1, IL-1α/IL-6, TNF-α/NF-κB, but not VCAM-1. Our results suggested that FRT enhanced radioprotection at least partially by regulating caspase 3/8-10, AIF, and PARP-1 to reduce apoptosis and by regulating ICAM-1, IL-1α/IL-6, TNF-α/NF-κB to reduce inflammation.

Radioprotection is an important approach to reduce the side-effects of radiotherapy. The radioprotective effect of the flavonoids of Rosa roxburghii Tratt (FRT) has been confirmed, and the mechanism has been identified as theBcl-2/caspase-3/PARP-1 signaling pathway. In this study, we investigated the effects of FRT on the intercellular adhesion molecule (ICAM), and vascular cell adhesion protein (VCAM) in addition to apoptosis-related proteins such as Bax/Bcl-2, p-ERK/ERK, p-p53/p53, and p-p38/p38. In the present study, we focused on the effect of FRT on PARP-1/AIF. Ionizing radiation triggered the activation of PARP-1 and AIF translocation from the mitochondrion to the nucleus. The inhibition of PARP-1/AIF signaling pathway by FRT was investigated. Our results showed that the expressions of Bax/Bcl-2, p-ERK/ ERK, p-p53/p53, and p-p38/p38 were decreased after FRT treatment compared with the radiation-treated group. FRT inhibited PARP-1 activation to inhibit AIF translocation from mitochondrion to nucleus. Pretreatment with FRT diminished the comet's tail and reduced fragments in six Gy-irradiated thymocytes compared with the irradiated cells without FRT treatment. We conclude that FRT enhanced radioprotection at least partially by regulating PARP-1/AIF to reduce apoptosis. J. Cell. Biochem. 118: 3943-3952, 2017. © 2017 Wiley Periodicals, Inc.

Radiotherapy is one of the most effective non-surgical treatments for many tumors. However, radiation damage remains a major negative consequence of radiotherapy. At present, radio-protective effect of troxerutin has been confirmed, but the mechanism of this radioprotection has not been elucidated. Here, this study showed that troxerutin protected thymus tissue of irradiated mice, and its radio-protective effect on thymocytes was significant in the range of 0.625-10μg/ml. Troxerutin significantly inhibited apoptosis of irradiated thymocytes at the concentration of 10μg/ml. Computer-aided drug design was used to investigate potential candidate targets for troxerutin, and an excellent correlation was identified between troxerutin and AKT (Pharm mapper and KEGG signal pathway). Troxerutin inhibited the activation of PTEN to stimulate AKT, which in turn prevented the activation of JNK to protect cells. Our results showed that troxerutin enhanced radioprotection at least partially by activating AKT to inhibit the activation of JNK.

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p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.