Domain-dependent Photodamage to Bcl-2

Tailor-made approach to photodynamic therapy in the treatment of cancer based on Bcl-2 photodamage.

It is very important to elucidate the mechanism of action and identify the molecular determinant of photodynamic medicine, in order to increase the number of clinical applications of photodynamic therapy (PDT) and perform personalized medicine. We have previously reported that PDT using some photosensitizers, such as phthalocyanine 4 (Pc 4) damages the anti-apoptotic protein Bcl-2, and that Bcl...

Role of caspase 3-dependent Bcl-2 cleavage in potentiation of apoptosis by Bcl-2.

Previous studies from our laboratory have demonstrated that Bcl-2 has a proapoptotic effect on neocarzinostatin (NCS)-treated PC12 pheochromocytoma cells. In the present study, we examine the mechanisms of this effect and demonstrate its relevance for the in vivo situation. Four hours after NCS treatment, a 23-kDa cleavage product of Bcl-2 was detected in whole cell lysates of bcl-2-transfected...

MCL-1–dependent leukemia cells are more sensitive to chemotherapy than BCL-2–dependent counterparts

Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are anti-apoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on Emu-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show th...

A Supplement to Photodamage

Antagonizing Bcl-2′s BH4 domain in cancer

cancer cells, including B-cell and lung cancers, display elevated expression of anti-apoptotic Bcl-2 proteins as a survival strategy to cope with oncogenic stress [1]. In cancer cells, Bcl-2 is loaded with pro-apoptotic BH3-only proteins, thereby not only preventing Bax/Bak activation but also rendering them " primed to death " at the mitochondria. The last decade, different compounds have been...