QUERCETIN EXHIBITS ANTI-TUMOR ACTIVITY IN AN IN VIVO MODEL OF KAPOSI’S SARCOMA

PRINCIPE GABRIEL; TIBURZI SILVINA; LEZCANO VIRGINIA; GARCIA BETINA N; GUMILAR FERNANDA; GONZÁLEZ PARDO VERÓNICA

Rosario

Congreso; LIX Congreso Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; 2023

SAIB

Quercetin (QUE) is a flavonoid with well-known anticancer properties, although its effect on viral-induced cancers is less studied. Kaposi’s sarcoma is a viral cancer caused by the human herpesvirus-8, which during its lytic phase expresses a constitutively activated G protein-coupled receptor (vGPCR) able to induce oncogenic modifications that lead to tumor development. Our previous work showed that QUE inhibits cell proliferation and promotes apoptosis in endothelial cells stably expressing vGPCR (vGPCR cells). To follow up with this research, the aim of this study was to evaluate the anti-tumor activity of QUE in an in vivo model of Kaposi’s sarcoma. For this purpose, tumor allografts from vGPCR cells were subcutaneously induced in N:NIH nu/nu mice. After 15 days of tumor development, mice were treated with QUE (50 or 100 mg/kg/d) or PBS (as control) administered by IP injection three times a week for 30 days. During the treatment, mice weight and behavior was monitored, and tumor volume was measured. The results showed that tumor progression was retarded in mice treated with QUE (100 mg/kg/d) compared to control (p < 0.001); whereas tumor weight was reduced by both QUE treatments (50 and 100 mg/kg/d) at the end of the test (p < 0.05 and p < 0.01, respectively). Immunohistochemical staining of tumors with the proliferation marker Ki67 showed that QUE treated tumors (50 and 100 mg/kg/d) exhibited a decline in proliferation compared to control (p < 0.05). In addition, serum biochemical parameters were measured to evaluate QUE toxicity. Neither kidney nor liver damage was detected since creatinine, alanine aminotransferase, and aspartate aminotransferase levels remained unchanged. Additionally, uremia was reduced by QUE treatment (50 and 100 mg/kg/d; p < 0.05, p < 0.01, respectively) and ALP levels decreased in mice treated with QUE (100 mg/kg/d) compared to control (p < 0.01). Moreover, a reduction in glycemia was found in mice treated with QUE (100 mg/kg/d) compared to control (p < 0.05), whereas not significant differences were found in total cholesterol and triglycerides. In conclusion, this study suggests that QUE exhibits antineoplastic activity and is devoid of toxic effects in an in vivo model of Kaposi’s sarcoma, being a suitable candidate for the treatment of this pathology.