title: Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced solid tumours.
abstract: Diet-derived flavonoids, in particular quercetin, may play advantageous roles by preventing or/and inhibiting oncogenesis. Evidence suggests that quercetin can elicit various properties depending on the cell type. The aim of this study was to evaluate its effects on Dalton's lymphoma ascites (DLA) induced solid tumours and to identify the target(s) of action. We addressed this question by inducing subcutaneous solid tumours in Swiss albino mice and investigated whether the quercetin affects essential biological processes that are responsible for tumour growth, morphology, angiogenesis and apoptosis. We also studied influence on several heat shock proteins (HSPs). Our findings demonstrate that intra-tumour administration of quercetin results in decreased volume/weight. Furthermore, we demonstrate that quercetin promotes apoptosis of cancer cells by down-regulating the levels of Hsp90 and Hsp70. Depletion of these two chaperones by quercetin might result in triggering of caspase-3 in treated tumours. Moreover, it also down-regulated the expression of major key angiogenic or pro-angiogenic factors, like HIF-1α and VEGF In addition, H and E staining together with immunofluorescence of fixed tumour tissue provided evidence in support of increased cell death in quercetin-treated mice.
authors.affiliation: Functional Genomics and Cancer Biology Laboratory, Center for Medical Engineering, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
authors.forename: Kushi
authors.initials: K
authors.lastname: Anand
authors.forename: Pallavi
authors.initials: P
authors.lastname: Asthana
authors.forename: Anup
authors.initials: A
authors.lastname: Kumar
authors.forename: Rashmi K
authors.initials: RK
authors.lastname: Ambasta
authors.forename: Pravir
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001202:Ascitic Fluid; D014408:Biomarkers, Tumor; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011794:Quercetin; D053148:Caspase 3