Cytotoxic T cell-induced apoptosis

Cytotoxic T lymphocytes and natural killer cells protect us against a variety of pathogens, and are involved in autoimmune diseases and transplant rejection. Granzyme B plays a major role in the mechanism used by these cytolytic effectors to destroy the target cells. This proteinase is produced by the effectors and stored within cytoplasmic granules. Upon interaction with the pathogenic cell the granzyme is transferred from the CTL to the target via directed exocytosis and subsequent receptor mediated endocytosis. It is interesting that cells that are deficient in expression of the receptor for granzyme are also resistant to CTL-     

Apoptin®-induced apoptosis: a review

Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/ or transformed cell lines, e.g. derived from breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma, cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.     

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy.     

Mitochondrial mechanism of cardiomyocyte apoptosis induced by stress

Stress induced the serious disorder of cardiac function and cardiovascular diseases. Apoptosis is the cellular basis in stress induced cardiac injury. In our previous study we found that many stressors resulted in mitochondrial damage. It is certain that mitochondria is important mediator in triggering apoptotic cell death, but the mechanism, by which the stress induced mitochondrial injury leads to cardiomyocyte apoptosis, remains unclear. We designed the present study to investigate the changes of the mitochondria in cardiomyocytes undergoing stress and its role in inducing apoptosis. Here we reported that stress changed the membrane fluidity of mitochondria and induced the lipid peroxidation of mitochondrial membrane in     

Can loss of apoptosis protect against cancer?

Cells of higher organisms can commit suicide in response to genomic alterations, a process called programmed cell death. Although it is commonly thought that the loss of programmed cell death is required for carcinogenesis, we argue that the situation is more complex and that the loss of programmed cell death can have the converse effect, preventing cancer progression. If the death rate of cancer cells is low, fewer cell divisions are required for the tumor to reach a certain size, resulting in the presence of fewer mutant cells. Therefore, the chances of overcoming potential selective barriers are reduced, rendering the failure of pathogenic progression probable. However, if there is a higher cell death rate, more cell divisions need to occur for the tumor to reach a certain size, resulting in the presence of more mutant cells and in an increased probability of overcoming selective barriers and cancer progression.     

Virus infections and apoptosis: Lessons from HIV

Many viruses establish life-long infections in their natural host with few if any clinical manifestations. The relationship between virus and host is a dynamic process in which the virus has evolved the means to coexist by reducing its visibility, while the host immune system attempts to suppress and eliminate infection without damage to itself. We are now beginning to understand that viruses can employ a variety of strategies to evade host immune responses. These include escape from T cell recognition, resistance to