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Chemotherapy induces tumor cell aging. (Cancer).

Researchers at the University of Illinois at Chicago have found that chemotherapy can permanently arrest the growth of tumor cells, countering a long-held view that the only way to stop cancer is to kill the proliferating cells. The tumor cells that stop dividing bear all the characteristics of senescent, or aged, cells, but that has both advantages and disadvantages. "Drug-induced arrest of cell division has long been considered only a stop-gap measure, because it was presumed the cells would eventually repair their damage and go on to divide again after treatment," explains Igor Roninson, professor of molecular genetics. "But we've found that many treated tumor cells that stop dividing don't start multiplying again later."

Investigators treated colon cancer cells with the commonly used anticancer drug doxorubicin. As happens with chemotherapy in cancer patients, some of the cells died, but others either survived and continued to grow or survived, but ceased dividing altogether. The cells that stopped dividing closely resembled normal cells that have lost their ability to grow because of senescence, the process of cellular aging. Many other cancer drugs besides doxorubicin also induce features of senescence in cancer cells, as does radiation therapy.

Using powerful genetic technology called cDNA microarrays, the researchers were able to identify molecular changes in the senescent colon cancer cells. Specifically, they found that the cells turned on multiple genes, of which approximately 10 were capable of halting cell growth. Some of them, known as tumor suppressors, function in normal cells, but are shut off when cancer develops. The onset of senescence reactivates these genes, shutting down cell division. Proteins encoded by some of the growth-inhibitory genes are known to act at a distance, stopping the growth of other tumor cells in the vicinity.

However, the senescent cells not only activated genes that inhibit cell division, they turned on genes that stimulate, rather than prevent, the growth of neighboring cells, as well as the p21 gene. The p21 turns on a host of genes linked to numerous diseases associated with old age, including Alzheimer's. Such genes were activated in the senescent colon cancer cells as well.
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Title Annotation:medical research
Publication:USA Today (Magazine)
Article Type:Brief Article
Geographic Code:1USA
Date:Oct 1, 2002
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