It's well know story Parylation(PAR) induced AIF mediated cell death.
In my case i observed hyper activation of PARP induced parylation (PARP level was decreased), Parylated protein was higly increased (PAR) after treatment with my drug. There was no cell death.
In this case how can i explain about the parylation. Normally parylation induced cell death.
Dear Pasupathi, we observed the same phenomenon in our breast cancer cell model, treated treated with Progesterone. We observed a hyper activation of PARP1 and an increase in PARylation but no AIF induced cell death. In our case the increase in PAR, mediated an a chromatin de-condensation, to aid access for chromatin remodellers and the displacement of histone H1 in order to facilitate hormone induced gene expression. Have you looked the the state of the chromatin, gene expression? Is the PAR a transient response?
Article PARty promoters: Hormone-dependent gene regulation requires ...
Dear Roni Wright, Thanks for your reply. Actually i am not working with epigenetic related work, but I eager to learn about epigenetic regulation in cancer.
I gone through your publication. I have some question to you,
After treatment PARP was disappeared (Like PARP1 inhibitor), I used cell signalling antibody (PARP) which we could not detect the PARP1 by western blot. So we decide our compound may disturb the antibody recognizing site, then we assumed parylation would be the reason, then we checked PAR by western blot, it was over expressed after treatment. over all PAR inhibitor or Parylation cause cell death. in my case no cell death why? as you said chromatin remodeling can cause cancer cell to normal cell through differentiation process, because after treatment the cell were not able induce tumorigenicity in xenograft model.
Now my target is to prove parylation (PARP1). And we tried to chechk PARP1 level by LC-MS, we could not make significant difference, in contrast western blot data showed very clear disappearance between control and treatment.
I hope you can give some more suggestion to make novel hypothesis with this concept.
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