Scientists in China have found a way to reset cancer cells' biological clock that could lead to new anticancer agents.

A corrole derivative that interferes with telomerase action

Cancer cells are distinguished from healthy cells by their ability to divide indefinitely. During normal cell division, telomeres, repeat DNA sequences at the end of chromosomes, shorten until they become too short for the cell to remain viable. But, in cancer cells this shortening is reversed by the enzyme telomerase, which is found in 80-90% of all cancers. Now, Xiang Zhou at Wuhan University and colleagues have synthesised two new corrole derivatives that interfere with telomerase action.

Telomeres are predominantly linear, but overhangs at the ends fold into structures called G-quadruplexes that block the action of telomerase. Zhou suggests that the group's corroles work by stabilising G-quadruplexes, as the corroles' positively charged planar ring structures bind to the negatively charged sugar-phosphate backbone of the telomere DNA.

Zhou also found that the corroles could induce G-quadruplex formation in the absence of the usual complement of cations found in cells. This has physiological implications because salt concentrations fluctuate in living cells. Corroles could therefore have a use in cancer treatment by inducing G-quadruplex formation under physiological conditions and so interfering with telomerase activity and cancer cell division.

Steven Rokita, a specialist in the therapeutic aspects of DNA modification at the University of Maryland, US, explained: 'Telomerase and telomeres are extremely attractive targets for anticancer chemotherapy since they control the life and death of individual cells. While there are a number of strategies to exploit these targets, stabilising G-quadruplexes is particularly attractive. The corrole system provides a very interesting new platform for this purpose and these cationic corrole derivatives have already exceeded the performance of the standard in the field, TMPyP4.'

Janet Crombie