Compound acts by rejuvenating ‘the guardian of the genome’. Skin cream tackles skin cancers in mice
Compound acts by rejuvenating ‘the guardian of the genome’.
药物通过恢复 “基因组卫士”---- p53蛋白的活力而发挥疗效。
A skin cream that can hyperactivate the body's natural DNA repair mechanisms has been shown to protect mice from skin cancer, and to reduce the growth of cancers already present. If the compound does the same for humans, it could one day be added to sunscreen as a cancer-fighting ingredient.
The active component of the cream, called CP-31398, works by reactivating disabled forms of a natural tumour-suppressing protein called p53. Nicknamed ‘the guardian of the genome’, p53 controls several important cellular functions, including the repair of damaged DNA, cell division and a genetically encoded auto-destruct pathway called apoptosis that kills unhealthy cells.
The p53 gene is mutated in over half of all human cancers. For that reason, pharmaceutical companies have been hunting compounds that can protect or restore p53 activity, in the hope that these might prevent or treat cancer.
In 1999, researchers at Pfizer showed that CP-31398 restores normal activity to mutated p53 proteins in cell cultures (although how exactly it works is a mystery)1. Mohammad Athar, a biochemist at the University of Alabama in Birmingham, went on to test the compound in live animals.
Athar and his colleagues slathered the compound onto the skin of hairless mice, and then exposed the mice to ultraviolet (UV) light twice a week for 35 weeks. At the end of the experiment, mice treated with CP-31398 had seven tumours on average; control mice that did not receive the drug had 16.
The tumours that did grow on treated mice were roughly a sixth the size of tumours in control mice. And, Athar and his colleagues found, the compound slowed the growth of preexisting skin tumours. The results are published this week in the Journal of Clinical Investigation 2.
“I think the results of this preclinical study look promising,” says Wafik El-Deiry, a cancer biologist at the University of Pennsylvania School of Medicine in Philadelphia. “If the compound survives subsequent testing it could be used as an additive to sunscreen.”
CP-31398 is not the first skin treatment that has been shown to repair cellular damage from sun exposure. Lotion containing fragments of DNA can ward off precancerous skin lesions in mice (see DNA-boosted sunscreen may fight cancer), and a salve containing a DNA repair protein reduces the number of skin tumours in people with a genetic defect in this DNA repair system. One important next step will be to compare how the cancer-fighting properties of CP-31398 compare not only to these experimental alternatives but also to the UV-blocking properties already in sunscreens, El-Deiry says.
作者:admin@医学,生命科学 2011-09-17 06:36