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Drug Combo Makes Cancer Cells Kill Themselves
Nov. 18, 1999
Reuters Health Information
NEW YORK -- A two-drug combination that pushes cancer cells to commit suicide can completely kill human tumors in laboratory experiments, U.S. researchers report.
Used in the proper sequence, these two drugs -- taxol and beta-lapachone -- "may represent a new therapy against human cancers," Dr. Chiang J. Li of the Dana-Farber Cancer Institute in Boston said in a hospital statement.
In experiments with human tumors, Li's team found that when the drugs were used together, or when the use of beta-lapachone was followed by the use of taxol, the drugs killed all of the cancer cells. The findings are published in the Nov. 9 issue of the Proceedings of the National Academy of Sciences.
Normally, the body's cells have a "checkpoint" system that alerts them to genetic damage. When the system goes awry, cells with genetic mutations are free to replicate and possibly lead to cancer. The combination of taxol and beta-lapachone seems to rebuild the checkpoint system in cancer cells.
Checkpoints serve as a type of 'quality control' for cells as they divide to form new cells. During each stage of division, cells pause at a checkpoint to make sure the genetic material in new cells will match the original exactly. If there is a genetic mutation, the cell normally either repairs the damage or kills itself to prevent the mutation from being passed on to its offspring.
In cancer cells, checkpoints fail to function. Li and colleagues aimed to restore checkpoints in cancer cells to see if this would force them to commit suicide. The researchers treated various types of human tumors with taxol and beta-lapachone, both known to act on particular cellular checkpoints. They found that the drugs caused several delays in cancer-cell division, signaling that the checkpoints had been re-established.
Moreover, the therapy caused cancer-cell suicide. Used alone, each drug triggered about half of the cells to kill themselves. Used together, however, the drugs caused all cells to die. The same was true when the researchers used beta-lapachone 24 hours ahead of taxol. The drugs showed equal effects on tumors of the ovaries, breast, colon, prostate, pancreas, lungs, and skin, according to the report.
The investigators note that the drug combination also wiped out human ovarian and prostate tumors that had been implanted in mice. Clinical trials are needed to see if it would do the same for cancer patients.
According to Li, this study "demonstrates that drug combinations that target the cell cycle at critical points can bring about cell death. This provides a framework for developing new drugs that may work in the same way." SOURCE: Proceedings of the National Academy of Sciences 1999;96:13369-13374.
c. Reuters News Service