Quercetin Displays Anti-Myeloma Activity and Synergistic Effect with Dexamethasone in Vitro and In Vivo Xenograft Models

Background: Multiple myeloma (MM) is a hematological malignancy with clonal plasma cell hyperplasia, which is still an incrurable disease since chemoresistance remains the major problem in MM management. Quercetin, a kind of dietary flavonoids, has shown its anticancer activity in many kinds of cancer cell lines and we tried to explore the effect of quercetin in MM.

Methods: In vitro, we examined the proliferation of MM cell lines(RPMI8226,ARP-1,MM1R) after treatment with quercetin combined with or without dexamethasone by MTT.Flow cytometry was used to detect apoptosis and cell cycle of MM cells induced by quercetin with or without dexamethasone.Then we detected mRNA and protein expression associated with apoptosis and cell cycle arrest by semiquantitative real time-polymerase chain (qRT-PCR)and western blot analysis. In vivo,a xenograft mice model of human myeloma was established and the mice received vehicle or quercetin alone or dexamethasone alone or quercetin combinded with dexamethasone, and the tumorburdern and the tumor tissue samples were analyzed by tumor volume and immunohistochemistry.

Results: Quercetin inhibited proliferation of MM cells by inducing apoptosis and cell cycle arrest in the G0/G1 or G2 phase(quercetin group vs control,p<0.05).Western blot showed that quercetin activated caspase3,caspase9,PARP-1 and increased cytochrome C release. C-myc and cyclinD1 expression were down-regulated and p21 were upregulated. Quercetinalso displays synergistic inhibition effect with dexamethasone in vitro (quercetin with dexamethasone vs quercetin only or dexamethasone only,p<0.05) and western bolt confirmed these results.In vivo,tumor burdern of xenograft mice modeltreated by quercetin was significantly lower than those of control(quercetin group vs control,p<0.05).

Conclusions: Quercetin inhibits proliferation of MM cells by inducing apoptosis and cell cycle arrest in the G0/G1 or G2 phase through downregulating c-myc and cyclinD1 and upregulating p21 .Quercetinalso displays synergistic inhibition effect with dexamethasone.Thus,quercetin combination with dexamethasone therapy may be an effective option for MM patients.