title: Silymarin and hepatocellular carcinoma: a systematic, comprehensive, and critical review.
abstract: The blessed milk thistle (Silybum marianum L.), a flowering plant native to Mediterranean Europe, has been consumed and extensively used as a cure for various chronic liver ailments over several centuries. Milk thistle extract, known as silymarin, is a complex mixture of seven major flavonolignans and one flavonoid. The phytoconstituents of silymarin owe their therapeutic and hepatoprotective effects to their strong antioxidant and anti-inflammatory properties. Primary liver cancer, also known as hepatocellular carcinoma (HCC), occurs in a milieu of oxidative stress and inflammation. The etiology of HCC includes chronic infection with hepatitis B and C viruses, cirrhosis, and exposure to dietary and environmental hepatocarcinogens. Current therapeutic options for HCC, including surgical resection and liver transplantation, have limited benefits and are essentially ineffective. Chemoprevention, using phytochemicals with potent antioxidant and anti-inflammatory properties, represents a fascinating strategy, which has been a subject of intense investigation in the recent years. In this review, we explore the potential role of silymarin as a chemopreventive and therapeutic agent for HCC. The review systematically evaluates the preclinical in-vitro and in-vivo studies investigating the effects of silymarin and its constituents on HCC. The biochemical mechanisms involved in the anti-liver-cancer effects of silymarin have been presented. The current status of clinical studies evaluating the potential of role of silymarin in liver cancer, especially that caused by hepatitis C virus, has also been examined. Potential challenges and future directions of research involved in the 'bench-to-bedside' transition of silymarin phytoconstituents for the chemoprevention and treatment of HCC have also been discussed.
authors.affiliation: aAmerican University of Health Sciences, Signal Hill bDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, California Northstate University, Elk Grove, California, USA cDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore dInterim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Jeanetta K
authors.initials: JK
authors.lastname: Mastron
authors.forename: Kodappully S
authors.initials: KS
authors.lastname: Siveen
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D020944:Silybum marianum / Q000737:chemistry; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D012838:Silymarin