Researchers Find that a Small Molecule Can Activate an Important Cancer Suppressor Gene

By activating a cancer suppressor gene, a small molecule called nutlin-3a can block cancer cell division, according to researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. This activation of the p53 gene leads to cellular senescence. An opportunity for new genetic mutations occurs each time a cell divides, so limiting the number of cell divisions in a cancer cell inhibits tumor progression.

Activation of p53 can suppress tumor growth through more than one mechanism. It can interfere with the cell cycle, prompting a cell with unrepaired DNA damage to commit suicide through a complex signaling pathway called apoptosis. Alternatively, p53 may trigger cellular senescence in response to DNA damage or cellular stress.

The expression of p53 is regulated by Mdm2, a protein that is overexpressed in several human cancers. Nutlins are small-molecule inhibitors that prevent the p53 protein from forming a complex with Mdm2, resulting in activation of p53. Previous studies have shown that nutlin can induce apoptosis in human cancer cells.

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