Quercetin as a Novel Therapeutic Approach for Lymphoma

Table 1

The effects of quercetin in treatment of lymphomas.

	Dose	In vitro/in vivo	Cell line	Effective molecular mechanism	Molecular targets of quercetin	Ref.
Large B-lymphomas	10 or 20 μM	In vitro	U937	Arrests cell cycle in the G2/M phase, increases cyclin B protein levels, and decreases cyclin D and E and E2F1 and E2F2 levels	Cyclin B, cyclin D, and cyclin E	[77]
	50 μM	In vitro	Daudi and TMD-8	Decreases expression of Notch1 protein	Notch1 protein	[78]
	—	In vitro	Namalawa	Arrest of cells in the G2/M phase	Caspase-3	[79]
	20 μM	In vitro	VAL, RL, and SUDHL-4 cell lines	Reduces expression of survivin and Mcl-1 and reduces restoration of the TRAIL pathway	TRAIL, Mcl-1	[80]
	20 μM	In vitro	DLBCL	Inhibits p-STAT3 and decreases expression of Mcl-1, survivin, and Bcl-x1 genes	STAT3 protein	[81]
	50 μM	In vitro	BC1, BC3, and BCBL1	Increases the number of G1 events; increases the inhibition of PI3K and mTOR kinase; reduces the Wnt activation pathway; decreases expression of c-FLIP, cyclin D1, c-Myc, and p65 NF-κB; reduces the release of IL-6 and IL-10; increases expression of HLA II (HLA-DR); decreases expression of HLA I	c-FLIP, cyclin D1, c-Myc, IL-6, IL-10, KSHV proteins, HLA-DR, and calreticulin	[59]
	50 mg	In vivo	—	Increases and decreases expression of the HIGD2A gene	Higd2a protein	[82]
Burkitt’s lymphoma	2.5, 10, and 25	In vivo	—	Inhibits primary viral antigens	Ornithine decarboxylase (ODC)	[83]
	30 μM	In vitro	Raji cell	Inhibits PI3Kδ; decreases expression of cIAP-1, cIAP-2, and anti-/proapoptotic molecules; inhibits the mTOR pathway; increases expression of the γH2A.X protein	PI3K and mTOR	[84]
	50 and 100 μM	In vitro	Raji, Akata, 2A8, Ramos, and BL-41	Inhibits c-Myc expression and the PI3K/AKT/mTOR pathway, reduces expression of HSP-70, and stimulates autophagy	c-Myc protein, PI3K, AKT, and mTOR	[60]
Multiple myeloma	100 and 200 μmol/L	In vitro	NCI-H929	Inhibits CDK4 expression; downregulates p-ERK and p-AKT; activates apoptosis-related proteins caspase-3, caspase-8, caspase-9, and PARP	Caspase-3, caspase-8, caspase-9, PARP, Bcl-2, P53, P21, P27, CDK4, p-ERK, and p-AKT	[85]
	40, 80, 160, and 320 μmol/L	In vitro	U266, KM3, RPMI8226, and MM	Downregulates IQGAP1 expression and p-ERK1/2 and inhibits the MAPK pathway in MM cells	IQGAP1 protein and ERK1/2	[86]
T-cell lymphoma	—	In vivo	—	Downregulates p-AKT, p-PDK1, p-BAD, p-GSK-3β, p-mTOR, p-IkBα, VEGF-A COX-2, iNOS, and NO level. Upregulates p-PTEN	AKT, PDK1, BAD, GSK-3β, mTOR, IkBα, VEGF-A, COX-2, iNOS, and PTEN	[87]
	300 μmol/L	In vitro	DLA	Downregulates p-AKT 1, p-PDK1, p-BAD, TNFR1, PKCα, and upregulates PTEN	AKT, PDK1, BAD, TNFR1, and PTEN	[88]