engleski

Chicken anemia virus derived protein apoptin triggers cell cycle arrest but not apoptosis in cancer stem cells

Chicken anemia virus-derived protein apoptin has the ability to kill human tumor cells, where it enters the nucleus and redirects cell signaling toward apoptosis by a still undefined mechanism. Normal cells are resistant to apoptin, where it accumulates in the cytoplasm. In the here presented study, antiproliferative activity of apoptin toward cancer stem cells (CSC) was compared to its effects toward other tumor cells. Transformed primary mammary epithelial cells (HMLE) with silenced gene for E cadherin (HMLE-shEcad) were used as the CSC model. An adenoviral vector that expresses Flag-tagged apoptin gene (Ad-Ap) and a control vector that expresses lacZ gene (Ad-LacZ) were used to infect cells. Localization within the cells, antiproliferative activity, different modes of programmed cell death, and cell cycle disturbances upon Ad-Ap infection were investigated. Although efficiency of transduction was low in the HMLE-shEcad cells, modest growth inhibition was measured. Apoptin localised in the nucleus of HMLE-shEcad cells, but it was not sufficient to induce apoptosis. Apoptin induced cell cycle G2 arrest 24 hours after infection, which delayed cell’s growth, but cells overcame this effect and recovered later. Apoptin showed distinct levels of cytotoxicity towards various tumor cell lines, identifying NCI-H1299 (non-small cell lung cancer) as the most sensitive. In these cells apoptin induced apoptosis, and also modulated autophagy. Our study confirmed apoptin as a potent tumor-cell killer, able to modulate different modes of programmed cell’s death, and moreover, to interfere with CSC. Mechanisms of CSC resistance to apoptin should be further analyzed and evaluated in more details.

Apoptin; apoptosis; cancer stem cells; cell cycle

nije evidentirano