Plant polyphenols for prevention and therapy of liver cancer

Abstract

Primary liver cancer, mainly hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths worldwide. The incidence of HCC is increasing worldwide; the overall survival of patients with HCC is grim because most patients are diagnosed late, when curative treatment is not possible and is the direct cause of about 1 million deaths annually. Chronic infection with hepatitis B viruses, toxic industrial chemicals, food additives (N-nitrosodiethylamine; NDEA), fungal toxins (aflatoxins), air, water pollutants and chronic heavy alcohol use leading to cirrhosis of the liver remain the most important causes. The great challenge in cancer prevention and control is how to manage those who have already been exposed to carcinogens, such as individuals who are HBsAg carriers and have long-term aflatoxin and NDEA exposure. The development of tumor markers that can detect HCC at even earlier stages is essential. In recent years, clinically useful tumor markers for HCC diagnosis have included α-fetoprotein (AFP), a fucosylated variant of the AFP glycoprotein which has a high affinity to the sugar chain of lens culinaris (AFPL3), des- γ-carboxy prothrombin (DCP), carcinoembryonic antigen (CEA) glypican-3 (GPC3) golgi protein 73 (GP73), growth factors or cytokines, insulin-like growth factor (IGF), interleukin (IL)-6 and IL-10, γ-glutamyl transferase (GGT) and α-L -fucosidase (AFU) etc. Chemoprevention has been proposed as the good tool to target these high-risk populations. Among various identified chemopreventive agents, plant polyphenols have been shown to be safe and high effective in inhibition of carcinogen-induced mutagenesis and tumorigenesis in bioassays and animal models for different target organ sites. The compounds derived from the plants are of considerable interest among oncologists. Many plant-derived, plant polyphenols have been studied for their chemopreventive and chemotherapeutic properties against human HCC, including green tea polyphenols, genistein (found in soy), apigenin (celery, parsley), luteolin (broccoli), quercetin (onions), kaempferol (broccoli, grapefruits), curcumin (turmeric), etc. The more we will discuss their involved molecular mechanisms and cellular targets, the better we could utilize these "natural gifts" for the prevention and treatment of HCC. Furthermore, better understanding of their structure-activity relationships will guide synthesis of analog compounds with improved bio-availability, stability, potency and specificity. In this article, for the sake of better understanding, the effective plant polyphenols against HCC will also be discussed, with more emphases on the basic conceptions of phenolics with strong antioxidant activity. ©2011 Nova Science Publishers, Inc. All rights reserved.