In vivo (Athens, Greece) · 2012
Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Kim Hyun, Bernard Mark E, Farkas Amy, Goff Julie, Kalash Ronny, Houghton Frank, Shields Donna, Franicola Darcy, Dixon Tracy, Zhang Xichen, Epperly Michael, Wang Hong, Cobanoglu Murat Can, Greenberger Joel S
Аннотация
BACKGROUND: Carbamazepine, a sodium channel blocker and pro-autophagy agent used in the treatment of epilepsy and trigeminal neuralgia, is also an ionizing radiation mitigator and protector.
MATERIALS AND METHODS: We measured the effect of carbamazepine, compared to other pro-autophagy drugs (i.e. lithium and valproic acid), on irradiation of autophagy incompetent (Atg5(-/-)) and competent (Atg5(+/+)) mouse embryonic fibroblasts, p53(-/-) and p53(+/+) bone marrow stromal cells, and human IB3, KM101, HeLa, and umbilical cord blood cell and in total body-irradiated or orthotopic tumor-bearing mice.
RESULTS: Carbamazepine, but not other pro-autophagy drugs, was a radiation protector and mitigator for mouse cell lines, independent of apoptosis, autophagy, p53, antioxidant store depletion, and class I phosphatidylinositol 3-kinase, but was ineffective with human cells. Carbamazepine was effective when delivered 24 hours before or 12 hours after total body irradiation of C57BL/6HNsd mice and did not protect orthotopic Lewis lung tumors.
CONCLUSION: Carbamazepine is a murine radiation protector and mitigator.
MATERIALS AND METHODS: We measured the effect of carbamazepine, compared to other pro-autophagy drugs (i.e. lithium and valproic acid), on irradiation of autophagy incompetent (Atg5(-/-)) and competent (Atg5(+/+)) mouse embryonic fibroblasts, p53(-/-) and p53(+/+) bone marrow stromal cells, and human IB3, KM101, HeLa, and umbilical cord blood cell and in total body-irradiated or orthotopic tumor-bearing mice.
RESULTS: Carbamazepine, but not other pro-autophagy drugs, was a radiation protector and mitigator for mouse cell lines, independent of apoptosis, autophagy, p53, antioxidant store depletion, and class I phosphatidylinositol 3-kinase, but was ineffective with human cells. Carbamazepine was effective when delivered 24 hours before or 12 hours after total body irradiation of C57BL/6HNsd mice and did not protect orthotopic Lewis lung tumors.
CONCLUSION: Carbamazepine is a murine radiation protector and mitigator.
Предметные рубрики MeSH
AnimalsAntioxidantsApoptosisAutophagyAutophagy-Related Protein 5CarbamazepineCarcinoma, Lewis LungCell Line, TumorCell SurvivalCells, CulturedClass I Phosphatidylinositol 3-KinasesFemaleFetal BloodFibroblastsGene Knockout TechniquesHematopoietic Stem CellsLithium ChlorideMembrane Potential, MitochondrialMiceMice, Inbred C57BLMicrotubule-Associated ProteinsNeoplasm TransplantationRadiation, IonizingRadiation-Protective AgentsTransplantation, HeterologousTumor BurdenTumor Suppressor Protein p53Valproic AcidWhole-Body Irradiation