title: Quercetin alleviates myocyte toxic and sensitizes anti-leukemic effect of adriamycin.
abstract: Objectives Derived from plants, flavonoids have been proven to possess anti-cancer activities. Adriamycin (ADM), an anthracycline antibiotic, is widely applied in the chemotherapy for leukemia; however, it has a side effect of heart damage. This study aims to explore potential anti-leukemia effects of quercetin (Que) and the underlying mechanism. Methods The P388 xenograft mice models were first established and then treated with Que alone or in combination with ADM. Subsequently, we evaluated their effects on cell proliferation and apoptosis by observing the cell cycle and detecting the Caspase-3 level, respectively. The underlying pro-apoptotic mechanism was further investigated by detecting the expression levels of NF-κB, Bcl-2, and Bax. The cardiomyocyte ultrastructural changes of P388 leukemic mice after drug treatment were also observed. The protective effect of Que on cardiomyocyte was evaluated by detecting enzymatic activity changes of glutathione peroxidase, superoxide dismutase, and malondialdehyde. Results Compared with ADM group, the combination of ADM and Que showed prolonged survival time and less peripheral white blood cells. Que could sensitize the anti-leukemic effect of ADM by inhibiting the proliferation of white blood cells through trapping the cells at the S phase; caspase-3 was activated via the expressional regulation of Bcl-2, Bax, and NF-κB. When applied in combination with ADM, Que could attenuate heart damage by cleaning the reactive oxygen species. Conclusion Our study may provide informative evidences for the underlying mechanism of anti-cancer effects of Que and sheds light on the clinical application of Que in leukemia treatment.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Han
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Junrui
authors.initials: J
authors.lastname: Wang
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Ren
authors.forename: Xiulan
authors.initials: X
authors.lastname: Su
authors.forename: Yingxu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; D011794:Quercetin; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione
keywords: Adriamycin; Leukemia; Myocyte damage; Quercetin; Xenograft nude mice