Quercetin Potentiates the Antitumor Activity of Rituximab in Diffuse Large B-Cell Lymphoma by Inhibiting STAT3 Pathway

  title={Quercetin Potentiates the Antitumor Activity of Rituximab in Diffuse Large B-Cell Lymphoma by Inhibiting STAT3 Pathway},
  author={Xin Li and Xinhua Wang and Mingzhi Zhang and Aimin Li and Zhenchang Sun and Qiwen Yu},
  journal={Cell Biochemistry and Biophysics},
STAT3 pathway plays an important role in the growth of diffuse large B-cell lymphoma (DLBCL) cells. Here we investigated the antitumor activity of Quercetin, a flavonoid compound, in combination with rituximab in DLBCL cell lines in vitro. We found that Quercetin synergistically enhanced rituximab-induced growth inhibition and apoptosis in DLBCL cell lines. Moreover, we found Quercetin exerted inhibitory activity against STAT3 pathway and downregulated the expression of survival genes. These… 
Quercetin as a Novel Therapeutic Approach for Lymphoma
It seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents, and highlighted the potential therapeutic effects of quercETin in various types of lymphoma.
The Central Role for Microenvironment in B-Cell Malignancies: Recent Insights into Synergistic Effects of its Therapeutic Targeting and Anti-CD20 Antibodies
The essential role of the tumor-associated niche in B-cell Lymphoma/Leukemia pathogenesis is outlined, in an attempt to optimize the use of microenvironment-targeted drugs and anti-CD20 antibodies in the various subsets.
STAT3 targeting by polyphenols: Novel therapeutic strategy for melanoma
The mechanisms of the STAT3 pathway regulation and their role in promoting melanoma, and the emerging data on polyphenols (PPs) specifically their contribution in melanoma therapies are evaluated with an emphasis on their regulatory/inhibitory actions in relation toSTAT3 pathway and current progress in the development of phytochemical therapeutic techniques.
Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer.
This review sheds some light on the importance of quercetin as an alternative therapeutic approach to this tumor, furthermore addressing the interplay between miRNAs and quERCetin in the regulation of apoptosis in ovarian cancer.
Effects of Rituximab on JAK-STAT and NF-κB signaling pathways in acute lymphoblastic leukemia and chronic lymphocytic leukemia
The preliminary results suggest that the use of Rituximab might be effective in B-ALL though both signaling pathways.
Evaluation of the antitumour activity of novel flavonoids on pre-clinical models of breast and ovarian cancer
There is accumulating evidence on the versatility of flavonoids and the numerous activities contributing to their anti-tumour effect, including extensive research on breast cancer.
Co-delivery of vincristine and quercetin by nanocarriers for lymphoma combination chemotherapy.
Flavonol Regulation in Tumor Cells
  • M. Lea
  • Biology
    Journal of cellular biochemistry
  • 2015
Therapeutic potential of flavonols is indicated by their growth inhibitory action accompanied by a decrease in several hallmarks of cancer such as resistance to apoptosis, and many investigators are sufficiently encouraged by past observations that they are responding to the challenge to optimize the dietary and therapeutic use of Flavonols in cancer prevention and treatment.
Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer
This review partitions this multicomponent review into how quercetin effectively regulates the Wnt/β‐catenin pathway, Janus kinase‐signal transducer and activator of transcription pathway, and vascular endothelial growth factor/vascular endothelial Growth factor receptor signaling cascade in different types of cancers, and provides an overview of the regulation of NOTCH and SHH pathways by quercETin.
Biosystem Analysis of the Hypoxia Inducible Domain Family Member 2A: Implications in Cancer Biology
The analysis of high definition expression profiles of HIGD2A suggests a role for HIG2A in cancer biology, and the relative quantification, by using qRT-PCR, showed that Higd2a expression is higher in bone marrow than in the liver or spleen.


STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B-cell lymphoma.
Direct inhibition of STAT3 with short hairpin RNA suppressed the growth of human ABC-like DLBCL in mouse models in a manner associated with apoptosis, repression ofSTAT3 target genes, and inhibition of a tumor-promoting microenvironment, suggesting that STAT3 inhibition may offer a promising approach in its therapy.
Rituximab inhibits the constitutively activated PI3K-Akt pathway in B-NHL cell lines: involvement in chemosensitization to drug-induced apoptosis
It is demonstrated for the first time that rituximab inhibits the constitutively activated Akt pathway in B-NHL cell lines, and this inhibition contributes to sensitization of drug-resistant cells to apoptosis by chemotherapeutic drugs.
Quercetin-mediated Mcl-1 and survivin downregulation restores TRAIL-induced apoptosis in non-Hodgkin’s lymphoma B cells
It is demonstrated that quercetin, a natural flavonoid, restores TRAIL-induced cell death in resistant transformed follicular lymphoma B-cell lines, despite high Bcl-2 expression levels due to the chromosomal translocation t(14;18).
Rituximab inhibits p38 MAPK activity in 2F7 B NHL and decreases IL-10 transcription: Pivotal role of p38 MAPK in drug resistance
Rituximab-mediated signaling identifies several new intracellular targets in NHL that may be of potential therapeutic interest for the development of new drugs in the treatment of drug-refractory NHL tumor cells.
Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma.
It is shown that inhibition of signal transducer and activator of transcription-3 (STAT3) leads to apoptosis in PEL cells, and suggested that activated STAT3 signaling directly contributes to malignant progression of PEL by preventing apoptosis, acting through the prosurvival protein survivin.
Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas.
The results define a second oncogenic pathway, STAT3 activation, which operates in ABC-DLBCL, suggesting that STAT3 may be a new therapeutic target in these aggressive lymphomas, and identify STAT3 as a novel BCL6 target gene.
Monoclonal antibody therapy for B-cell non-Hodgkin's lymphoma.
The current uses of monoclonal antibodies in B-cell non-Hodgkin's lymphoma are reviewed to provide options for patients with refractory disease.
The STATs of cancer — new molecular targets come of age
Tumour cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. STAT proteins — especially STAT3 and STAT5 — regulate all of
Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition.
  • D. FerryA. Smith D. Kerr
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1996
In conclusion, quercetin can be safely administered by i.v. bolus at a dose injection and evidence of antitumor activity was seen.