Carbohydrate trap for cancer
doi:10.1038/nindia.2011.181 Published online 12 December 2011
Researchers have developed a new carbohydrate-conjugated heterobimetallic complex that has successfully killed laboratory samples of colon and breast cancer cells. The heterobimetallic complex could therefore yield cures for breast and colon cancers.
Metal-based chemotherapeutic drugs have received much attention since the discovery of cisplatin, which contains platinum. However, platinum-based drugs have toxic side-effects on the kidneys, nerve cells and the gastrointestinal tract. In addition, cancer cells have grown resistant to cisplatin. Unfortunately, cancer cells have so far demonstrated poor uptake of bimetallic complexes, thus reducing the effectiveness of such compounds as anticancer agents.
Attaching carbohydrate molecules to metallic complexes may increase their uptake by cancer cells because cancer cells consume significant amounts of glucose. To investigate this potential, the researchers developed a carbohydrate-conjugated heterobimetallic complex containing copper and tin. They used N glycoside, a carbohydrate molecule derived from D glucosamine hydrochloride.
Anticancer agents first permeate cancer cells and then destroy the DNA whose activity drives the cancer cells' proliferation. This is why the researchers first looked at the metallic complex's ability to bind to DNA using calf thymus DNA. The positively charged core of the heterometallic complex bound to the negatively charged phosphate backbone of DNA through electrostatic attraction. The tin demonstrated a preferential selectivity for oxygen atoms in the phosphate of the DNA helix, thereby disintegrating the DNA structure.
In studies with plasmid DNA isolated from Escherechia coli, the complex cleaved double-stranded supercoiled plasmid DNA after 1 h of incubation at physiological pH 7.2. When tested against 20 different cancer cell lines, the complex showed good toxic effects on human colon and breast cancer cells.
"Attaching carbohydrate to the heterobimetallic complex will increase its uptake by cancer cells, thus reducing toxic effects and sparing normal cells," says lead researcher Sartaj Tabassum.
- Tabassum, S. et al. Carbohydrate-conjugate heterobimetallic complexes: synthesis, DNA binding studies, artificial nuclease activity and in vitro cytotoxicity. Carbohydr. Res. 346, 2886-2895 (2011)