Quercetin induces cell apoptosis of myeloma and displays a synergistic effect with dexamethasone in vitro and in vivo xenograft models
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Donghua He1,*, Xing Guo1,*, Enfan Zhang1, Fuming Zi2, Jing Chen1, Qingxiao Chen1, Xuanru Lin1, Li Yang1, Yi Li1, Wenjun Wu1, Yang Yang1, Jingsong He1, Zhen Cai1
1Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
2Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
*These authors contributed equally to this work
Zhen Cai, email: firstname.lastname@example.org
Keywords: apoptosis, dexamethasone, multiple myeloma, quercetin
Received: February 23, 2016 Accepted: May 28, 2016 Published: June 14, 2016
Quercetin, a kind of dietary flavonoid, has shown its anticancer activity in many kinds of cancers including hematological malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and MM) in vitro and in vivo. However, its effects on MM need further investigation. In this study, MM cell lines were treated with quercetin alone or in combination with dexamethasone. In order to observe the effects in vivo, a xenograft model of human myeloma was established. Quercetin inhibited proliferation of MM cells (RPMI8226, ARP-1, and MM.1R) by inducing cell cycle arrest in the G2/M phase and apoptosis. Western blot showed that quercetin downregulated c-myc expression and upregulated p21 expression. Quercetin also activated caspase-3, caspase-9, and poly(ADP-ribose)polymerase 1. Caspase inhibitors partially blocked apoptosis induced by quercetin. Furthermore, quercetin combined with dexamethasone significantly increased MM cell apoptosis. In vivo xenograft models, quercetin obviously inhibited tumor growth. Caspase-3 was activated to a greater extent when quercetin was combined with dexamethasone. In conclusion, quercetin alone or in combination with dexamethasone may be an effective therapy for MM.
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