Cell death was once thought to be a passive non-specific event, but is now known to be an active
biochemical process. Scientists have discovered that any cells have the ability to die by this process, called programmed cell death or apoptosis.
A number of important human diseases are caused by abnormal apoptosis control mechanisms, which can result in either a pathological increase in the number of cells (e.g. cancer) or a damaging loss of cells (e.g. degenerative diseases). Recent data has shown that cells have a discrete cell death pathway defined by a specific set of genes. These genes encode proteins that form the biochemical process that ultimately invokes cell death.
The key genes that control the cell death process are the cell death effectors of the CED-3/ICE ("caspase") family and the cell death inhibitors of the Bcl-2 family. The caspase gene family encodes a set of proteases responsible for carrying out the death process. In a living cell, these proteases are normally kept inactive by proteins encoded by the Bcl-2 family.
Small molecule drugs, like CHML, are able to specifically modulate the activity of the caspase family, the Bcl-2 family, or other key points in the apoptotic pathway, and exert control over the cell death process and have utility in diseases characterized by either excessive or insufficient levels of apoptosis.
p53 protein, commonly referred to as "the tumor suppressor gene," is a key player in the cellular apoptosis process. Bio-therapeutic activation of this pathway has been a popular target for recent drug discovery technology.
p53, Bax and p21 protein levels were measured by immunoblotting assay, in MCF-7, ML-1, H1299 (human lung carcinoma) and RKO (human colon cancer,) cell lines after treatment with CHML. p53 protein was found to be elevated in the MCF-7, RKO and ML-1 cells.
As the ability to induce apoptosis is not limited to p53 positive cell lines, it appears that CHML is able to provoke apoptosis through both p53-dependant and -independent pathways.