What processes could cause a cell (here LNCaP prostate cancer cells) to enlarge to 10 - 15 times their size? They have been treated with a tyrosine kinase inhibitor. They still appear to be quite viable, adhere well, and have viable mitochondria when treated with MTT. No visible apoptosis, and no visible necrosis or cell disintegration. There is some evidence of enlarged vesicles but not in all affected cells.
Alwyn Dart
I will try to put my answer very simplistically, like an overview.
Cell division occurs in three steps: Karyosynthesis, Karyokinesis and Cytokinesis. After division, the daughter cells will be rather smaller, but grows during the G0 phase. If there is cytokinesis block, and the other two are OK, then multinucleated cells develop. If there is both karyokinesis and cytokinesis block and karyosynthesis is OK, then a cell with large nucleus (hyperchromatic too) occurs with high N/C ratio. But if the cell is very slowly proliferating, then cytoplasm too can get enough time to enlarge, resulting in large cells.
Tyrosene kinase can inhibit both Karyokinesis and Cytokinesis. And the LNCaP prostate cancer cells are rather very slow growing compared to other prostate cell types, I believe. Hence they can become enlarged for the above given reason. This slow growth rate is also the probable reason for lack of apoptosis, necrotic death.
I would suggest you to measure the the nuclear DNA content and other endpoints by Flow cytometry which may be helpful.
Narayanan
Dear Dr. Alwyn Dart
The enlargement of cancer cells could be because of genotoxic stress. The presence of chemotherapeutic drug (tyrosine kinase inhibitor) can cause damage to DNA, triggering the formation of enlarged cells known as polyploid giant cancer cells. These cells are formed because of endoreplication (duplicating chromosomes without cell division), mitotic slippage (failure to properly separate chromosomes during mitosis), or cytokinesis failure (failure to divide the cell into two daughter cells). Also, the cell cycle checkpoints, which are mechanisms that ensure the accuracy of cell division, are disrupted, leading to the accumulation of chromosomes in cells resulting in polyploidy.
Regards,
Malcolm Nobre
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