Apoptosis and Cancer

Apoptosis, or programmed cell death, is a natural mechanism in which a damaged cell dies in order to prevent further damage to the multicellular organism. The absence of apoptosis in damaged cells can lead to many types of cancers and other diseases. In certain types of cancers, a family of proteins, known as the Bcl-2 family, has been observed as being over-expressed compared to normal, healthy cells.^[1]

Bcl-xl is a specific protein of the Bcl-2 family that, when over-expressed, may act as an initiator of tumor formation. There is also evidence to suggest that Bcl-xl expression may also contribute to chemo-resistance. The protein includes seven and no beta sheets.

Inhibition of the over-expression of the Bcl-2 family of proteins has been shown to be effective at inducing tumor regression and increasing chemo-sensitivity. This represents the binding of an to the anti-apoptotic protein, .

The ligand is a member of the family. ABT-737 has been shown to effectively inhibit the over-expression of this protein thereby inducing tumor regression and increasing chemo-sensitivity.

Shown here is the interaction between the ligand and the protein via . The hydrogen bond is formed between an oxygen from the sulfoxone portion of the drug to an "N-H" group of a glycine amino acid. This forms one of the intermolecular or "weak" bonds between the drug and protein.

Shown here is a sort of formed between the protein (red) and hydrophobic, or "water hating", portions of the acyl-sulfonamide. This is an example of hydrophobic bonding formed by intermolecular forces between some hydrophobic sections of the protein with hydrophobic portions of the ligand.

Click on each amino acid to view the hydrophobic interactions with the ligand: