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

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Abstract

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.

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Abbreviations

DMBA:

7,12 Dimethylbenz(α)anthracene

DCIS:

Ductal carcinoma in situ

ER:

Oestrogen receptor

H&E:

Haematoxylin and eosin

HCC:

Hepatocellular carcinoma

IDC:

Infiltrative ductal carcinoma

ILC:

Infiltrative lobular carcinoma

LI:

Labelling index

PCNA:

Proliferating cell nuclear antigen

SCH:

Schizophyllan

TAM:

Tamoxifen

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Acknowledgments

The present study was supported by the Swedish Research Links (VR) to E. Aleem and by an institutional grant from the city for scientific research and technology applications to A. Daba.

Conflict of interest

The authors declare that they have no conflicts of interests.

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Author notes

  1. Ayman Daba

    Present address: Fertility and Cryogenics Lab, Downers Grove, IL, 60516, USA

Authors and Affiliations

  1. Department of Zoology, Division of Molecular Biology, Faculty of Science, Alexandria University, Moharram Bey, Alexandria, 21511, Egypt

    Ahmed Mansour & Eiman Aleem

  2. Department of Biochemistry, Faculty of Science, Alexandria University, Moharram Bey, Alexandria, 21511, Egypt

    Muhammed El-Saadani

  3. Department of Pathology, Faculty of Medicine, Alexandria University, Azarita, Alexandria, 31211, Egypt

    Nahed Baddour

  4. Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications (MuCSAT), New Borg El Arab, Alexandria, Egypt

    Ayman Daba

  5. Cancer Center Karolinska, Department of Oncology Pathology, CCK R8:04, Karolinska Institutet, 171 76, Stockholm, Sweden

    Eiman Aleem

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Supplementary material 1 (JPG 294 kb)

432_2012_1224_MOESM2_ESM.tif

Supplementary material 2. Caspase-3 labelling index in comparison with the apoptotic index in mammary gland and liver. In general increase in the percentage of apoptotic cells was associated with an increase in caspase-3 expression in comparison with control (a) Histogram showing the effect of different drug treatments (x-axis) on the caspase-3 labelling index (LI) in the mammary gland (y-axis) in comparison with the apoptotic index by TUNEL assay. Data are expressed as mean ± standard deviation. DMBA treatment increased the caspase-3 LI by 128-fold, while SCH resulted in twofold increase in comparison with control. Treatment of mice bearing DMBA-initiated tumours with TAM upregulated the caspase-3 LI by twofold in comparison with DMBA. Black columns indicate the percentage of apoptotic cells by TUNEL assay, grey columns indicate the caspase-3 labelling index, (b) Histogram showing the effect of different drug treatments (x-axis) on the caspase-3 labelling index (LI) in liver (y-axis). Data are expressed as mean ± standard deviation. SCH resulted in twofold increase in caspase-3 labelling in comparison with DMBA. Black columns indicate the percentage of apoptotic cells by TUNEL assay and grey columns indicate the caspase-3 labelling index. (TIFF 235 kb)

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Mansour, A., Daba, A., Baddour, N. et al. Schizophyllan inhibits the development of mammary and hepatic carcinomas induced by 7,12 dimethylbenz(α)anthracene and decreases cell proliferation: comparison with tamoxifen. J Cancer Res Clin Oncol 138, 1579–1596 (2012). https://doi.org/10.1007/s00432-012-1224-0

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