Schizophyllan inhibits the development of mammary and hepatic carcinomas induced by 7,12 dimethylbenz(α)anthracene and decreases cell proliferation: comparison with tamoxifen

• Published in: Journal of cancer research and clinical oncology 2012-09, Vol.138 (9), p.1579-1596
• Main Authors: Mansour, Ahmed, Daba, Ayman, Baddour, Nahed, El-Saadani, Muhammed, Aleem, Eiman
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic agents; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Breast cancer; Cancer Research; Caspase 3 - metabolism; Cell Proliferation - drug effects; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gynecology. Andrology. Obstetrics; Hematology; Herbal medicine; Immunohistochemistry; Internal Medicine; Liver cancer; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Mammary gland diseases; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - metabolism; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mice; Mushrooms; Oncology; Original Paper; Pharmacology. Drug treatments; Proliferating Cell Nuclear Antigen - metabolism; Receptors, Estrogen - metabolism; Rodents; Schizophyllum - chemistry; Sizofiran - administration & dosage; Sizofiran - pharmacology; Survival Analysis; Tamoxifen - administration & dosage; Tamoxifen - pharmacology; Tumors
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-012-1224-0

Background Breast cancer is one of the leading causes of cancer mortality among women. Some anticancer compounds have been isolated from mushrooms. The aim of the present work was to study the anticancer effects of schizophyllan (SCH), a β- d -glucan extracted from the mushroom Schizophyllum commune alone or in combination with tamoxifen (TAM) on 7, 12 Dimethylbenz(α)anthracene (DMBA)-induced carcinomas in mice. Methods We isolated SCH from S. commune . Female mice received DMBA, SCH, DMBA+SCH, DMBA+TAM or DMBA+TAM+SCH or vehicles. We studied mice survival, tumour incidence, histopathology, oestrogen receptor (ER) expression, cell proliferation by immunohistochemical detection of proliferating cell nuclear antigen (PCNA), apoptosis by TUNEL assay, as well as caspase-3 expression. Results DMBA treatment resulted in mammary and hepatocellular carcinomas (HCC). Both SCH and TAM reduced the incidence of DMBA-induced mammary tumours by 85 and 75 %, respectively, and equally decreased the PCNA labelling index relative to DMBA. TAM treatment increased the incidence of- and PCNA index in HCCs relative to DMBA, while SCH suppressed these effects. TAM was more effective than SCH in the induction of apoptosis in both mammary and hepatic carcinomas. Caspase-3 levels correlated with the apoptotic index in most experimental groups. Conclusions Only one dose of SCH had similar therapeutic effects against DMBA-induced mammary carcinomas as 4 weeks of TAM treatment. This coupled with the ability of SCH to suppress hepatic lesions associated with TAM treatment provides the rationale for further investigating the combined therapeutic effects of TAM+SCH in preclinical models of ER-positive breast cancer, as well as in liver cancer.