Cancer Preventive Agents. 7. Antitumor-Promoting Effects of Seven Active Flavonolignans from Milk Thistle (Silybum marianum.) on Epstein-Barr Virus Activation

Abstract Seven pure flavonolignans were isolated from an extract of milk thistle [Silybum marianum.(L.) Gaertn (Asteraceae)], by semipreparative reverse-phase HPLC, and identified based on spectroscopic and LC-MS/IT-TOF data. All seven compounds were screened as potential antitumor-promoting agents by using the in vitro. short-term 12-O.-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. They showed good inhibitory activity (87.7–94.9%) at 1000 mol ratio/TPA. Silychristin A (1) and silychristin B (2) were slightly more potent than the well-known antitumor promoter β.-carotene. Silychristins A (1) and B (2) and isosilybins A (6) and B (7) were more active than the clinically proven cancer prevention components silybins A (4) and B (5).

[1]  Shishir Shishodia,et al.  Molecular targets of dietary agents for prevention and therapy of cancer. , 2006, Biochemical pharmacology.

[2]  K. Kowdley,et al.  A review of Silybum marianum (milk thistle) as a treatment for alcoholic liver disease. , 2005, Journal of clinical gastroenterology.

[3]  H. Nishino,et al.  Inhibitors of skin-tumor promotion. VIII. Inhibitory effects of euglobals and their related compounds on Epstein-Barr virus activation. (1). , 1990, Chemical & pharmaceutical bulletin.

[4]  H. Rosen,et al.  Milk Thistle (Silybum marianum) for the Therapy of Liver Disease , 1998, American Journal of Gastroenterology.

[5]  W. Smith,et al.  A silychristin isomer and variation of flavonolignan levels in milk thistle (Silybum marianum) fruits. , 2005, Planta medica.

[6]  R. Agarwal,et al.  Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. , 1999, Cancer letters.

[7]  W. Henle,et al.  Immunofluorescence in Cells Derived from Burkitt's Lymphoma , 1966, Journal of bacteriology.

[8]  R. Agarwal,et al.  Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. , 2005, European journal of cancer.

[9]  D. Y. Lee,et al.  Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). , 2003, Journal of natural products.

[10]  S. Luper,et al.  A review of plants used in the treatment of liver disease: part 1. , 1998, Alternative medicine review : a journal of clinical therapeutic.

[11]  C. Gluud,et al.  Milk Thistle for Alcoholic and/or Hepatitis B or C Liver Diseases—A Systematic Cochrane Hepato-Biliary Group Review with Meta-Analyses of Randomized Clinical Trials , 2005, The American Journal of Gastroenterology.

[12]  Harukuni Tokuda,et al.  Cancer Preventive Agents. Part 5. Anti-tumor-Promoting Effects of Coumarins and Related Compounds on Epstein-Barr Virus Activation and Two-stage Mouse Skin Carcinogenesis , 2006 .

[13]  S. Katiyar.  Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (Review). , 2005, International journal of oncology.

[14]  Y. Chawla,et al.  Herbal Medicines for Liver Diseases , 2005, Digestive Diseases and Sciences.

[15]  V. Lawrence,et al.  Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. , 2002, The American journal of medicine.

[16]  R. Agarwal,et al.  A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients , 2006, Investigational New Drugs.

[17]  M. Roma,et al.  Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medication. , 2006, Current medicinal chemistry.

[18]  Harukuni Tokuda,et al.  Cancer Preventive Agents. Part 6: Chemopreventive Potential of Furanocoumarins and Related Compounds , 2006 .