Published on December 12, 2005 at 4:16 PM
It seems that while PP2A suppression occurs in other forms of cancer, Perrotti said their tests reveal that in CML, it only occurs in the blast crisis, and in the initial, chronic phase of the disease.
Perrotti remembered from earlier studies that forskolin could restore PP2A function; however although forskolin is currently used in Japan as a broncho- and vaso-dilator and has been tested and found safe in clinical trials in Austria among patients with asthma, it has not been approved by the FDA for use in the United States.
In their research Perrotti and his team tested the effects of forskolin on normal, Gleevec -sensitive and Gleevec-resistant CML cells, and discovered that the extract restored normal PP2A function, reduced the cancer cells' ability to grow by up to 90 percent and induced leukemic cell death and differentiation.
In the meantime it had no adverse effects upon normal cells.
The team found that when leukemic mice which had been treated with forskolin then stopped getting the treatment, some died of leukemia and others showed evidence of Bcr-Abl activity.
But once the forskolin treatment was resumed, even weeks after the initial treatment had stopped, Bcr-Abl activity was blocked and normal cell functioning was reinstated.
Perrotti says forskolin may well be an additional or potential treatment for patients with CML who have already advanced to the blast phase, but more pre-clinical and pharmacologic studies need to be done to assess the therapeutic relevance of forskolin in patients with leukemia.
The research is published in the November issue of Cancer Cell.