Because our objective was to test

Because our objective was to test selleck chemicals llc the hypothesis that ceramide analogs are effective apoptosis sensitizers for Fas mediated apoptosis in human colon carcinoma cells, we chose LCL85 for this study. Next, Inhibitors,Modulators,Libraries eleven human colon carcinoma cell lines were cul tured in the presence of a sublethal dose of LCL85 and various doses of FasL, and analyzed for tumor cell viability. Four of the 6 primary colon carcinoma cell lines are highly sensitive to FasL induced apoptosis, and LCL85 exhibited minimal or no sensitization effects on these 4 sensitive cell lines. On the other hand, the other 2 primary human colon carcinoma cell lines RKO and SW116 are resistant to Fas mediated apoptosis. However, LCL85 also only exhibited minimal or no sensitization Inhibitors,Modulators,Libraries effects on these 2 cell lines.

One of the 5 metastatic human colon carcinoma cell lines is sensitive to FasL induced apoptosis, but Inhibitors,Modulators,Libraries 4 of Inhibitors,Modulators,Libraries the 5 metastatic human colon carcinoma cell lines are resistant to Fas mediated apoptosis. A sub lethal dose of LCL85 significantly increased these 4 meta static human colon carcinoma cell lines to FasL induced apoptosis. In summary, our data demonstrated that a sublethal dose of LCL85 is effective in sensitizing the apoptosis resistant human colon carcinoma cells to Fas mediated apoptosis. Next, we used SW620 and LS411N cells to determine whether the above observed tumor cell growth inhi bition is due to apoptosis. SW620 and LS411N cells were cultured in the presence of LCL85 and FasL, and analyzed for apoptosis. Staining cells with Annexin V and PI revealed that LCL85 induces apoptosis of SW620 and LS411N cells in a dose dependent manner.

However, LCL85 alone at low doses only induced a small degree of apoptosis. In contrast, a sublethal dose of LCL85 dramatically increased SW620 and LS411N Inhibitors,Modulators,Libraries cell sensitivity to FasL induced apoptosis. To determine whether LCL85 sensitized apoptosis is tumor type dependent, we also tested the effects of LCL85 on metastatic human breast cancer cells. MDA MB 231 cells were treated with various doses of LCL85 in the absence or presence of FasL and analyzed for apoptosis. As in the human colon carcinoma cells, LCL85 induced MDA MB 231 apoptosis in a dose dependent manner, albeit at a low degree. MDA MB 231 cells are new product resistant to FasL induced apoptosis, and LCL85 is effective in sensitizing MDA MB 231 cells to FasL induced apoptosis at a dose of 25 uM. These observa tions thus suggest that a sublethal dose of ceramide analog LCL85 is a potent apoptosis sensitizer. LCL85 increases cellular C16 ceramide level to sensitize colon carcinoma cells to apoptosis We next treated SW620 cells with a sublethal dose of LCL85 and measured the level of cellular ceramides and ceramide metabolites.

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