Caffeic acid phenethyl ester derivative exerts remarkable anti-hepatocellular carcinoma effect, non-inferior to sorafenib, in vivo analysis

Abstract

Abstract Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we investigated CAPE derivative 1ʹ (CAPE 1ʹ) monotherapy to HCC, compared with sorafenib. HCC Bel-7402 cells were treated with CAPE 1ʹ, the IC50 was detected using CCK-8 analysis, and acute toxicity testing (5 g/kg) was performed to evaluate safety. In vivo, tumor growth after CAPE 1ʹ treatment was evaluated using an subcutaneous tumor xenograft model. Five groups were examined, with group 1 given vehicle solution, groups 2, 3, and 4 given CAPE 1ʹ (20, 50, and 100 mg/kg/day, respectively), and group 5 given sorafenib (30 mg/kg/day). Tumor volume growth and tumor volume-to-weight ratio were calculated and statistically analyzed. An estimated IC50 was 5.6 µM. Acute toxicity tests revealed no animal death or visible adverse effects with dosage up to 5 g/kg. Compared to negative controls, CAPE 1ʹ treatment led to significantly slower increases of tumor volume and tumor volume-to-weight. CAPE 1ʹ and sorafenib exerted similar inhibitory effects on HCC tumors. CAPE 1ʹ was non-inferior to sorafenib for HCC treatment, both in vitro and in vivo. It has great potential as a promising drug for HCC, based on effectiveness and safety profile.

Keywords

• Hepatocellular carcinoma
• Caffeic acid phenethyl ester derivative
• Sorafenib
• Non-inferiority
• In vivo analysis