Chemo combination kills breast cancer stem cells

The drugs don't work separately, but together -- and often combined with the drug tamoxifen -- they prevent mutations that allow breast cancer to reproduce and spread.
By Stephen Feller   |   May 2, 2016 at 3:50 PM

AUGUSTA, Ga., May 2 (UPI) -- Two chemotherapy drugs that are ineffective on their own killed breast cancer stem cells when combined to treat rodent and human cancer cells, researchers report in a new study.

The drugs, 5-azacytidine and butyrate, are often used together with other cancer treatments to reduce recurrence, with researchers at Augusta University finding their efficacy is tied to normalizing gene expression in stem cells expected to turn cancerous and spread beyond the breast.

Researchers at Augusta University have previously shown 5-azacytidine's ability to inhibit DNMT1, which reduces levels of the ISL1 gene -- a control mechanism for stem cells and natural tumor suppressor. In the previous study, when DNMT1 was blocked, 80 percent of breast tumors were eliminated.

Butyrate, which is present at high levels in breast milk, blocks the signaling molecules RAD51AP1 and SPC25. The two molecules ordinarily help repair DNA but are often over-expressed in cancer, as well as because of some cancer treatments, enabling and aiding the spread of cancer cells.

The new study suggests getting at stem cells may help doctors more effectively fight cancer, the researchers say.

"Most current chemotherapy does not kill the stem cells, which are the cells of origin, only the tumor mass," Dr. Muthusamy Thangaraju, a biochemist in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia and Georgia Cancer Center at Augusta University, in a press release.

For the study, published in the journal Cancer Research, the researchers tested the drugs, combined and separately, in mouse models of breast cancer and cell lines from human breast cancer patients.

The researchers found the combination of drugs affected the ways stem cells make breast cancer, including by preventing the mutations that enable its spread away from the breast. The finding helps understand why the pair can, when used with the chemotherapy tamoxifen, prevent recurrence of breast cancer, they said.

"This combination might need to be considered for all breast cancer patients because their common denominator is cancer stem cells," Thangaraju said.

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