Beating cancer immunity
doi:10.1038/nindia.2008.339 Published online 22 December 2008
A new hybrid molecule has shown promise in halting unbridled growth of breast cancer cells immune to existing anti-cancer drugs. The molecule containing short chain fatty acid (SCFA) and monosaccharide inhibits cancer cell proliferation by suppressing a gene and a few proteins linked to breast cancer1.
The researchers selected the cancer drug candidate per-butanoylated N-acetyl-D-mannosamine (Bu4¬ManNAc) and treated a special type of breast cancer cells (MDA-MB-231) with it. The cancer cells exposed underwent controlled death over a two-week period. The molecule also suppressed the expression of a cancer gene known as MUC1 (mucin1) known to aid cancer cell growth. Further, it reduced the activity of proteins like matrix metalloprotinease-9 (MMP-9), CXCR4 (a cell surface receptor), and NF-κB, associated with breast cancer.
The key to the molecule's success as an anti-cancer agent lies in the presence of an N-acyl group at the second carbon and ester-linked SCFA group at the sixth carbon, which are thought to initiate anti-cancer activities.
The study lays the foundation of a highly versatile platform to exploit the emergence of carbohydrates as scaffolds for drug discovery. It also holds promise in intensifying efforts to develop therapies for invasive breast cancer, the researchers say.
The authors of this work are from: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, US and Laboratory of Chemical Glycobiology, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
- Campbell, T. C. et al. Targeting Pro-Invasive Oncogenes with Short Chain Fatty Acid-Hexosamine Analogues Inhibits the Mobility of Metastatic MDA-MB-231 Breast Cancer Cells. J. Med. Chem. 51, 8135-8147 (2008) | Article |