SULFORAPHANE SUPPRESSES HEPATOCELLULAR CARCINOMA IN MICE VIA ACTIVATING p53, MITIGATING OXIDATIVE STRESS, AND INHIBITING ANGIOGENESIS.
TL;DR
SF decreased the number of tumor nodules and ameliorated HCC by activating p53 expression, inducing apoptosis, and inhibiting proliferation, oxidative stress, and angiogenesis, and support further translational evaluation of SF as a potential therapeutic agent for HCC.
Abstract
Background
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Sulforaphane (SF) is a natural isothiocyanate that exhibits anticarcinogenic activity against various cancer cells in vivo and in vitro, with no observed side effects. It also has a prophylactic effect against early stages of some cancer models, including HCC. The study aimed to assess the therapeutic anticarcinogenic effect of SF in experimental murine HCC in vivo and to estimate possible underlying mechanisms of its effects on cell proliferation, angiogenesis, and antioxidant status.
Materials And Methods
HCC was induced in mice by a single intraperitoneal dose of 100 mg/kg of diethylnitrosamine, followed by 22 weekly intraperitoneal doses of 0.5 mg/kg of carbon tetrachloride. After the induction of HCC, SF (2 mg/kg body weight) was given orally from weeks 25 to 28. Then we conducted histopathological examination, biochemical analysis of blood sera, and immunohistochemical analysis of marker expression in liver sections.
Results
SF improved liver structure and function in HCC-bearing mice and survival rate, significantly reduced the expression of tumor marker alpha-fetoprotein and the number of hepatic nodules, and downstaged HCC. These changes were accompanied by an increase in total antioxidant capacity, expression of p53 and Bax, as well as a significant decrease in lipid peroxidation and immunoreactivity of PCNA, VEGF, and Bcl-2 in liver tissues.
Conclusion
SF decreased the number of tumor nodules and ameliorated HCC by activating p53 expression, inducing apoptosis, and inhibiting proliferation, oxidative stress, and angiogenesis. These findings support further translational evaluation of SF as a potential therapeutic agent for HCC.