Our results indicated selleck chem that D6 treatment may promote a block of cell cycle progression in G2 phase and this could represent one of the mechanisms that in hibit melanoma cells growth, as previously observed. Alterations in cell cycle progression are indeed important events in cancer development and hindering such altered mechanism has Inhibitors,Modulators,Libraries been often used as a good strategy to in hibit tumour growth. To investigate the possible molecular mechanisms trig gered by D6 treatments, we undertook a gene expression profile analysis on melanoma cancer cells and fibroblast normal cells. Our primary objective was to identify genes that were up or down regulated in response to treatment, and which could be related to the phenotypic outcome.

Two lists of regulated transcripts, one for LB24 melanoma cells and the other for BJ fibroblasts Inhibitors,Modulators,Libraries were selected and subsequently analyzed Inhibitors,Modulators,Libraries by the IPA software. Considering both the most significant functional categories Inhibitors,Modulators,Libraries and canon ical pathways, the activity of D6 compound in melanoma cells Inhibitors,Modulators,Libraries is certainly based on either cell stress responses either activation/repression of mechanisms regulating cell survival. Pathway analysis re vealed up regulated effectors of cell stress response and protein degradation as well as down regulated gene prod ucts controlling cell proliferation. The acti vation of cell defence pathways observed on melanoma cells indicates that D6 treatment causes important stimulation of the cellular stress re sponse, with a strong induction of HSPs, which in turn af fects cell survival and drives toward cell death.

In physiological or pathological selleck chem inhibitor conditions, cellular stress leads to transport and accumulation of damaged proteins in the endoplasmic reticulum where they should be repaired or committed to degradation. This stimulates the over expression of chaperons and HSPs that perform a sort of quality control and drive seriously damaged proteins to ubiquitination and proteasome degradation. When endo plasmic reticulum functions are strongly compromised, this organelle triggers apoptotic signals in order to eliminate the irreversibly damaged cell. In our model, several HSPs genes show to be up regulated, and HSPA6 is the most over expressed transcript. It codifies for the stress inducible Hsp70B protein, normally under expressed or absent in most cell types, whose expres sion is strictly linked to that of Hsp72 . both these proteins have a key role in me diating cell survival during endoplasmic reticulum proteotoxic stress conditions. One could speculate that their huge increase of expression levels following D6 treat ment could be related to the extreme endoplasmic reticulum stress response that finally directs melanoma cells to death by triggering apoptosis.