Possible ameliorating effect of isoquercetin on diethylnitrosamine-induced hepatocellular carcinoma in albino mice

Abstract

ABSTRACT The majority of cases of liver cancer are discovered late in the disease’s progression, making it the third leading cause of cancer death globally. Chemotherapy is the major treatment choice for advanced stages of hepatocellular carcinoma (HCC); however, drug resistance, adverse effects, and high cost are major problems for effective treatment. Isoquercetin (IQ) is a dietary flavonoid, which has an anti-proliferative effect against several cancer cell lines. It also has a prophylactic effect against the early stages of some cancer models including HCC. The purpose of this study was to assess the therapeutic anticarcinogenic effect of IQ against murine HCC. A single intraperitoneal (ip) dose of 100 mg/kg of diethylnitrosamine (DEN), followed by 18 weekly ip doses of 0.5 mg/kg of carbon-tetrachloride (CCl4) was used to induce HCC. After the induction of HCC, IQ (10 and 20 mg/kg bw) was given orally from week 21 to week 24. IQ most likely ameliorated the structure and function of livers with experimentally induced HCC by improving the survival rate, significantly reducing tumor marker alpha-fetoprotein (AFP), number of hepatic nodules and downstaging HCC. This was accompanied by an increase in endogenous antioxidant capacity and the tumor suppressor protein ‘p53’, as well as lower levels of the lipid peroxidation marker malondialdehyde (MDA), proliferation marker proliferating cell nuclear antigen (PCNA) and angiogenesis marker vascular endothelial growth factor (VEGF) in the tissues. IQ suppresses proliferation, oxidative stress, and angiogenesis in advanced HCC by activating the tumor suppressor protein p53 and inhibiting proliferation, oxidative stress, and angiogenesis.