User:Eottergonzalez/sandbox



apoptosis in cervical tumor derived cell lines

Viral proteins can cause intracellular stress which induces apoptosis in cells.This response to internal stimuli causes a caspase cascade which in turn triggers a series of morphological changes within the cell. Once the caspase cascade has started, it is an irreversible process resulting in certain cell death. Canine distemper virus (CDV) is known to cause apoptosis in central nervous system and lymphoid tissue of infected dogs in vivo and in vitro. Apoptosis caused by CDV is typically induced via the extrinsic pathway which activates caspases that disrupt cellular function and eventually leads to the cells death. In normal cells CDV activates caspase-8 first which works as the initiator protein followed by the executioner protein caspase-3. However apoptosis induced by CDV in HeLa cells does not involve the initiator protein caspase-8. HeLa cell apoptosis caused by CDV follows a different mechanism than in vero cell lines. This change in the caspase cascade suggests CDV induces apoptosis via the intrinsic pathway, excluding the need for the initiator caspase-8. The executioner protein is instead activated by the internal stimuli caused by viral infection not a caspase cascade.

Apoptosis in HeLa cells is inhibited by proteins produced by the cell, these inhibitory proteins target retinoblastoma tumor suppressing proteins. These tumor suppressing proteins regulate the cell cycle, but are rendered inactive when bound to an inhibitory protein. HPV E6 and E7 are inhibitory proteins expressed by the human papillomavirus, HPV is responsible for the formation of the cervical tumor from which HeLa cells are derived. HPV E6 causes p53, which regulates the cell cycle, to become inactive. HPV E7 binds to retinoblastoma tumor suppressing proteins and limits its ability to control cell division. These two inhibitory proteins are partially responsible for HeLa cells immortality by inhibiting apoptosis to occur. CDV is able to induce apoptosis despite the presence of these inhibitory proteins. This is an important oncolytic property of CDV, this virus is capable of killing canine lymphoma cells. Oncoproteins E6 and E7 still leave p53 inactive, but they are not able to avoid the activation of caspases induced from the stress of viral infection. These oncolytic properties provided a promising link between CDV and lymphoma apoptosis which can lead to development of alternative treatment methods for both canine lymphoma and human non-Hodgkin lymphoma. CDV's ability to induce apoptosis could play an important role in developing treatments for tumor cells resistant to radiation and chemotherapy. Defects in the cell cycle are thought to be responsible for certain tumor cells resisting chemotherapy or radiation, so a virus that can induce apoptosis despite defects in the cell cycle is useful for cancer treatment.