Newly identified compound induces apoptosis in AML cells
Scientists from Albert Einstein College of Medicine and Dana-Farber Cancer Institute find a compound that induces apoptosis -- a form of programmed cell death -- in acute myeloid leukemia (AML) cells.
Notably, the compound does not affect normal cells. This is very important because many existing chemotherapic agents have a risk of side effects.
The study, "Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia," appears in the latest issue of the journal Cancer Cell.
Dr. Evripidis Gavathiotis at Albert Einstein College of Medicine is the corresponding author. He hopes that the newly identified compound will more effectively treat cancer and cause fewer side effects.
Dr. Gavathiotis is committed to discovering molecular mechanisms of cell death and cell survival regulation with the goal to develop novel therapeutic strategies for cancer and other diseases.
The BCL2-associated X protein, or BAX, is a central activator of apoptosis. When activated, BAX pokes holes in mitochondria, causing the release of pro-apoptotic factors. However, cancer cells often use anti-apoptotic factors to inhibit BAX and therefore survive.
Prior to this work, Dr. Gavathiotis and colleagues solved the structure of BAX's activation site. They then searched compounds that could potently activate BAX. In this work, they showed that one of the candidate compounds, which they named BTSA1, is a potent BAX activator.
BTSA1 effectively promoted apoptosis in human AML cell lines as well as in AML patient samples. When tested in mice grafted with human AML cells, BTSA1 greatly prolonged the survival of the mice. Notably, no adverse effects were observed.
The researchers also discovered that the levels of BAX were much higher in AML cells from patients than in normal blood cells from healthy people. This explains why BTSA1 effectively induce apoptosis in AML cells but not in normal cells.
In the future, the team will investigate whether BTSA1 would be useful in treating other cancers.
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