Markers of sensitivity to polyamine depletion in cancer
Non-proliferating cells have low levels of polyamines and stimulation of cell proliferation always results in an increase in the polyamine pools. Treatment of cells with compounds that deplete the cellular polyamine pools always results in growth inhibition and sometimes this is followed by apoptosis. Because of this, compounds that deplete the cellular polyamine pools are being considered in cancer treatment. Our research has shown that normal cells are much less sensitive to polyamine depletion than cancer cells. However, the sensitivity among cancer cells differs substantially.
We are using a number of cancer cell lines of breast cancer (MCF-7, SK-BR-3, JIMT1, MDA-MB-231, HCC1937 and L56Br-C1) and neuroblastoma (SH-SY5Y, LA-N-1 and IMR-31) origin.
Protein markers for sensitivity testing
We are concentrating on proteins involved in the regulation of the cell cycle and apoptosis and that favor cell survival. Protein levels are investigated using Western blot. Some representative proteins are cyclins and their associated cyclin dependent kinases as well as cyclin dependent kinase inhibitors. In the apoptotic pathway, proteins of the three main subgroups of Bcl-2 family will be investigated. Of interest are also proteins involved in signal transduction pathways and cell cycle check-point controls.