The effect of caffeic acid phenethyl ester analogues in a modified resistant hepatocyte model

Abstract

We present a study of the chemoprotective effects of two caffeic acid phenethyl ester (CAPE)-related structures: LQM717 and LQM706. The modified resistant hepatocyte model in rats was used to study the chemoprevention of these CAPE analogues, which are inexpensive and easily obtained. In the liver cancer model used, we detected extensive necrosis and lipid peroxidation after 24 h, many altered hepatic foci, putatively preneoplastic lesions with γ-glutamyl transpeptidase staining after 30 days, and liver tumors at 12 months. We tested the effect of the CAPE analogues on necrosis, lipid peroxidation, proliferation, p65 activation, altered hepatic foci, and tumors. Both compounds exerted protective effects on lipid peroxidation, necrosis, cell proliferation, p65 activation, and preneoplastic lesions. Rats under a carcinogenic protocol showed a 52, 71.74, and 51.6% decrease in the number of preneoplastic nodules when pretreated with CAPE, LQM706, and LQM717, respectively. At 12 months after carcinogenic treatment, eight of eight rats developed liver cancer, whereas in the group of rats that received pretreatment with CAPE, LQM706, or LQM717, 62.5, 83.3, or 42.85%, respectively, had tumors. In conclusion, LQM717 has the potential to enhance chemoprotection activity much better than CAPE by markedly reducing the formation of liver cancers in this model, and this is a compound that is easy to obtain.

Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: A review on its anti‐inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects

“…This suggests the potential merit of CAPE in delaying age‐related hepatocellular changes. Macias‐Perez et al showed that CAPE exhibits protection against lipid peroxidation, necrosis, aberrant cell proliferation and p65 activation. Rats under a carcinogenic protocol ( N ‐diethylnitrosamine) showed decreased number of preneoplastic nodules and reduced incidence of liver tumors when pretreated with CAPE.…”

Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma

“…The effects of these compounds on lipid peroxidation are attributed to the direct antioxidant activity (chelating properties and ROS decrease) of CAPE and the indirect antioxidant activity (inhibition of the metabolism or induction of the antioxidant system in the cells) of their analogs. In addition, the three compounds act by decreasing the activation of p53, NFkB activator (apoptosis-related transcription factor, proliferation and cell cycle) (80).…”

Phenolic Acids of Plant Origin—A Review on Their Antioxidant Activity In Vitro (O/W Emulsion Systems) Along with Their in Vivo Health Biochemical Properties

“…Dietary supplementation of rats, with CA and CAPE (5 mg/kg body wt subcutaneous or 20 mg/kg oral), was shown to inhibit tumor growth in HCC cells (HepG2) and reduce the tumor invasion at a liver metastatic site [91]. Another clinical study [92] has reported a clear chemoprotective effect of CAPE and its analogs (20 mg/kg body wt) against lipid peroxidation and subsequent cell proliferation of hepatic tumors (HCC) in rats.…”

“…CA chemoprotective effect on cell proliferation, p56 activation of hepatic tumors (HCC). [92] CA (100 mg/kg) in the rat microbiota CA reduce certain biomarkers that indicate liver injury [96] Carnosic acid (CarA)…”