Cell membrane permeability and defective G2/M block as factors potentially contributing to increased cell...

Immortalized mammalian cell lines are a valuable research tool, though they represent a highly simplified model. Due to accumulated mutations they may not reflect characteristics of the disease or even the tissue they derive from.

We aim to pinpoint factors distinguishing SeAx cells from two other cutaneous T-cell lymphoma (CTCL) cell lines, namely Hut78 and MyLa2000. Of note, these factors may influence cell sensitivity in an unspecific way and therefore should be taken under consideration.

We evaluated transcriptional levels of drug transporters across cell lines, cell membrane permeability, functionality of pathways related to DNA damage response and activation of G2/M block.

Analysis of the transcriptional levels of genes coding drug efflux pumps indicated that they are not consistently down-regulated in SeAx. However, we noted that SeAx cell membrane is markedly more permeable than Hut78 and MyLa2000, which may contribute to increased chemosensitivity in an unspecific way.Moreover, though DNA damage response seemed to be at least partly functional in SeAx cells, they fail to activate G2/M block in response to psoralen + UVA treatment. Any DNA damage should be repaired before cells enter mitosis, in order to uphold genome integrity. Thus, a defective cell cycle block may contribute to cell sensitivity.

We believe that factors such as increased membrane permeability or defective cell cycle block should be accounted for when comparing sensitivity of cell line panels to chemotherapeutics of interest. It is worth to exclude a simple, indiscriminative mechanisms of cell resistance or sensitivity before attempting comparisons. Cell lines that are indiscriminately sensitive to a broad range of chemicals may contribute to overestimating the cytotoxic potential of tested compounds if used in cytotoxicity studies.