Fig 6. Possible cell fate under oxidative stress.

Prolonged oxidative stress (ROS) leads to severe cell damage and depletion of cell energy reserves. Nevertheless, many cell injuries caused by ROS could be sublethal, especially because PC-3 cells have non-functional p53 and therefore disrupt the triggering of apoptosis. Even if a damaged cell is driven to oncosis, reversion of this process is possible, particularly if the cell is able to restore ATP production. A way to gain enough energy for survival could be autophagy. Similar to autophagy, digestion of the cytoplasm of neighbouring cells can provide a source of amino acids. Retention of a foreign nucleic acid by cannibalistic engulfment could result in aneuploid or polyploid state. Furthermore, reduction in membrane and cell stiffness due to protein catabolism by autophagy could reflect increased entotic activity. Cell in cell structure results in the decreased surface-to-volume ratio, thereby minimizing cell membrane requirements. Furthermore, a live cell internalized by entosis could disrupt host cell division. Subsequently, cytokinesis often fails, which can lead to the formation of polyploid giant cancer cells (PGCCs). PGCCs often dye by apoptosis or senescence, but a small fraction of these cells is able to survive and even produce aneuploid progeny. Senescence, polyploidy and self-renewal seem to be three steps to immortality of cancer cells. Autophagy could play an important role in all of them.