The finding, published in the July 6 issue of the Proceedings of the National Academy of Sciences, explains a beneficial side effect of lovastatin which underscores the proteasome as a target for cancer prevention. The drug s known mode of action is to inhibit the cholesterol biosynthesis pathway. Khandan Keyomarsi, Ph.D., and her team in the State Health Department s Wadsworth Center laboratories have discovered that the commonly prescribed form of the drug also inhibits the proteasome pathway. The proteasome pathway is an intracellular garbage disposal for proteins that are no longer needed or are malformed. CKIs act as brakes on cell division, and in their absence cancer s hallmark of runaway cell proliferation can occur.
Cancer cells have low or undetectable levels of CKIs when compared to normal cells.
Dr. Keyomarsi s team treated human breast cancer cells with lovastatin and observed an increase in levels of two CKIs, p21 and p27. The increase prevented the further proliferation of the tumor cells. A 1993 study of patients taking the drug to lower high cholesterol found a 33 percent reduction in their incidence of all cancer types, compared to the expected rate. A more recent report of test tube and animal studies suggested that it deters colon cancer. Neither investigation explained how the medication's known mode of action might account for its association with lower cancer incidence.