The BCL-2 protein family plays a central role in cell death regulation by diverse mechanisms, including apoptosis and autophagy. This family includes the anti-apoptotic proteins BCL-2, BCL-W, BCL-XL, MCL-1 and A1, and is intensively studied as a target for pharmacological intervention in cancer. Senescent cells have been reported to be resistant to extrinsic and intrinsic pro-apoptotic stimuli. A study set out to evaluate the individual contributions of each of these BCL-2 family members and their combinations to the viability of senescent cells. It found that the increased presence of BCL-W and BCL-XL underlies senescent cell resistance to apoptosis, and that their combined inhibition leads to senescent cell death. It show that a small-molecule inhibitor targeting the BCL-2, BCL-W and BCL-XL proteins (ABT-737) causes preferential apoptosis of senescent cells, both in vitro and in vivo, and eliminates these cells from tissues, opening the door for targeted elimination of senescent cells.
Another study investigated the expression and role of Bcl_xL in human hepatocellular carcinoma (HCC). The Bcl_xL protein was expressed in HepG2, Hep3B, and Huh7 human hepatoma cell lines at high levels, but none of these cells expressed Bcl_2. Bcl_xL was expressed in all 20 surgically resected human HCC tissues when examined by Western blot analysis and immunohistochemistry, and levels of its expression were higher in a subset of HCC tissues than those of adjacent nontumor liver tissues or normal livers. The study concluded that Bcl_xL expressed in human HCC cells inhibits apoptosis produced by various cellular stresses, such as staurosporine treatment, serum starvation, and p53 activation, and may play an important role in their survival.
© 2006-24 MyBioSource.com.
All rights reserved.
Privacy Policy | Terms & Conditions