Dairy milk fat augments paclitaxel therapy to suppress tumour metastasis in mice, and protects against the side-effects of chemotherapy

  • Xueying Sun
  • Jie Zhang
  • Rita Gupta
  • Alastair K. H. MacGibbon
  • Barbara Kuhn-Sherlock
  • Geoffrey W. Krissansen
Research Paper

Abstract

Milk fat is a natural product containing essential nutrients as well as fatty acids and other food factors with reported anti-cancer potential. Here bovine milk fat was tested for its ability to inhibit the growth of breast and colon cancers and their metastasis to the lung and liver; either alone or in combination with the chemotherapeutic agent paclitaxel. A diet containing 5% typical anhydrous milk fat (representing ~70% of the total dietary fat component) fed to Balb/c mice delayed the appearance of subcutaneous 4T1 breast and CT26 colon cancer tumours and inhibited their metastasis to the lung and liver, when compared to the control diet containing soybean oil as the only fat component. It augmented the inhibitory effects of paclitaxel on tumour growth and metastasis, and reduced the microvessel density of tumours. It displayed no apparent organ toxicity, but instead was beneficial for well-being of tumour-bearing mice by maintaining gastrocnemius muscle and epididymal adipose tissue that were otherwise depleted by cachexia. The milk fat diet ameliorated gut damage caused by paclitaxel in non-tumour-bearing mice, as evidenced by retention of jejunal morphology, villi length and intestinal γ-glutamyl transpeptidase activity, and inhibition of crypt apoptosis. It prevented loss of red and white blood cells due to both cancer-mediated immunosuppression and the cytotoxic effects of chemotherapy. The present study warrants the use of milk fat as an adjuvant to inhibit tumour metastasis during cancer chemotherapy, and to spare patients from the debilitating side-effects of cytotoxic drugs.

Keywords

Angiogenesis Breast cancer Cachexia Chemotherapy Colon cancer Immunosuppression Metastasis Milk fat Mucositis Paclitaxel Soybean oil 

Abbreviations

AMF

Anhydrous milk fat

CLA

Conjugated linoleic acid

DMBA

7,12-Dimethyl-benz(a)anthracene

FAME

Fatty acid methyl ester

γ-GGT

γ-Glutamyl transpeptidase

TUNEL

Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling

9-HSA

9-Hydroxystearic acid

SCFA

Short-chain fatty acids

Notes

Acknowledgments

This work was supported by a grant from the Foundation for Research, Science, and Technology, New Zealand, and supported by Fonterra, New Zealand, and Auckland Uniservices Ltd. We thank Yvonne van der Does for the preparation of the milk fat samples.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Xueying Sun
    • 1
    • 2
  • Jie Zhang
    • 1
    • 2
  • Rita Gupta
    • 1
    • 2
  • Alastair K. H. MacGibbon
    • 1
    • 3
  • Barbara Kuhn-Sherlock
    • 1
    • 3
  • Geoffrey W. Krissansen
    • 1
    • 2
  1. 1.Lactopharma Consortium, University of AucklandAucklandNew Zealand
  2. 2.Department of Molecular Medicine & Pathology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  3. 3.Fonterra Research CentrePalmerston NorthNew Zealand

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