Serendipity strikes cancer cells

Researchers at the University of NSW looking for a protein analysis tool have accidentally come up with a drug that can halt cell growth in tumours.

The researchers, at the UNSW Centre for Vascular Research (CVR), were developing a metronomic compound to indicate the effectiveness of disulphide bond cleavage in proteins.

However, when the compound -- a peptide trivalent arsenical dubbed GSAO -- was tested on certain tumours, it was noticed that the cells stopped multiplying.

"It was serendipity really," said CVR group leader, Prof Philip Hogg. "We made this compound to do one thing -- which it did quite well, incidentally -- but realised it had these other properties too. So we ended up looking at that instead,".

The GSAO compound inhibits tumour angiogenesis and tumour growth in mice by inactivating mitochondria in angiogenic endothelial cells. Hogg said the compound works by entering the cells and affecting the protein so that the cell dies.

"This in turn stops blood cell and vessel generation, so the tumour stops growing. It doesn't affect quiescent cells, only active ones, so it doesn't destroy the tumour. But it does ensure the growth of the cancerous cells does not continue," he asserted.

Hogg described the new compound as a "kind of mitochondrial poison". He said that GSAO, which is small, synthetic, non-toxic and orally-available, should be extremely attractive as a commercially exploitable drug, if trials prove it suitable.

"The compound is ready for Phase I and II trials, and the IP holders [UNSW tech transfer company] will approach interested pharma once these have been satisfactorily completed. We are ready to go on the trials, and have already arranged with a producer to manufacture the compound," he said.

"What we have done is to effectively found a way to knock out growing cells. This points the way to other paths we could take to kill other kinds of cells. We are already looking at the way these compounds work on arthritis with positive results, and think psoriasis will be next," he added.

The research is published in the latest issue of the journal Cancer Cell.