Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Japan, responsible for over thirty thousand deaths per year.1 Diagnostic imaging for HCC in its early stage has progressed including contrast-enhanced ultrasound and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB) MRI. Therapeutic options for HCC including radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), surgical resection and molecular-targeted therapy (Sorafenib), have also increased. Despite these advances in diagnosis and treatment, the prognosis of patients with HCC remains unsatisfactory.2 In order to improve the outcomes of patients with HCC, novel chemopreventive and therapeutic compounds are urgently required. Geraniol is a natural acyclic monoterpene contained in the essential oils of many aromatic plants such as geranium and lemon.3 It is widely used as an aromatic component in many cosmetic products. In addition to its aromatic properties, geraniol has been reported to demonstrate anti-tumor activity in a variety of cancer cells including lung,4 pancreatic,5 colon6 and liver.7 The mechanisms of anti-cancer effects of geraniol include inhibition of angiogenesis3 and the mevalonate pathway,4 modulation of the Ras-extracellular signal-regulated kinase (ERK) signaling pathway8 and inhibition of NF-κB,9 then leading to the modulation of cellular proliferation and apoptosis. However, little is known about geraniol inhibiting hepatocarcinogenesis in vivo. Diethylnitrosamine (DEN) is an established hepatocarcinogen in rats.10 DEN has been reported to induce hepatocarcinogenesis by alteration of the DNA structure, formation of alkyl DNA adducts and induction of chromosomal aberrations and micronuclei in the liver.11 In the present study, we evaluated anti-hepatocarcinogenic effects of geraniol in DEN-induced hepatocarninogenic rats.