Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats

• Published in: PloS one Vol. 9; no. 10; p. e110145
• Main Authors: Jie, Meng, Cheung, Wan Man, Yu, Vivian, Zhou, Yanling, Tong, Pak Ho, Ho, John W S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.10.2014; Public Library of Science (PLoS)
• Subjects: Animals; Anticancer properties; Antineoplastic Agents - pharmacology; Antiproliferatives; Apoptosis; Bcl-2 protein; Biology and Life Sciences; Cancer; Carcinogens; Carcinogens - toxicity; Cell cycle; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Enzymes; G1 phase; G1 Phase Cell Cycle Checkpoints - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Glucosinolates - pharmacology; Health aspects; Hepatocytes; Hepatotoxicity; Humans; Laboratory animals; Life sciences; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver cancer; Liver Neoplasms - chemically induced; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Medical treatment; Medicine and Health Sciences; Metabolism; Metastases; Nutrition; Oral administration; p53 Protein; Prognosis; Proto-Oncogene Proteins c-mdm2 - genetics; Rats; Rats, Sprague-Dawley; Resting Phase, Cell Cycle - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Sinigrin; Toxicity; Tumor cells; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumors; Xenograft Model Antitumor Assays; Hong Kong; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110145

Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.