These findings additionally indicate increased apoptotic activity upon vorinostat treatment. Discussion Uterine sarcomas are very rare malignancies with poor prognosis. Precise diagnosis is usually made late, these tumors frequently grow highly aggressive and are resis tant to chemotherapy. Thus, surgical excision is often the only treatment new post option. Molecularly targeted therapies of different tumor types showed a promising improvement in the last few years. Histone deacetylases, a group of enzymes responsible for epigenetic changes of histones and some other proteins, belong to the most promising targets. Some inhibitors of these enzymes are already used in preclinical and clinical trials. Vorinostat efficiently inhibits Inhibitors,Modulators,Libraries HDACs class I and II by binding to the active site of the enzyme.
However, vorinostat seems to have different effects depending on the cell line used. While in most experimental systems vorino stat caused apoptotic changes, there Inhibitors,Modulators,Libraries are also data show ing that autophagic processes are activated by vorinostat. Vorinostat has been already approved by FDA for the therapy for cutaneous T cell lymphoma. That makes it also an interesting candidate for the treatment of other malignancies. However, data con cerning gynecological malignancies in general and uter ine sarcoma in particular are missing. Here we attempted to establish a uterine sarcoma cell model for testing vorinostat in vitro and in vivo. For this purpose MES SA cell line was used since it has been shown that these cells are tumorigenic in nude mice.
In fact, after injecting 5 106 MES SA cells into nude mice, tumor growth has been induced with 100% effi ciency. Our intention was also to use this model as an alternative for endometrial stromal sarcoma. Immuno histochemical comparison of MES SA and ESS 1 cells proved that these two cell lines are quite similar regard ing different cell markers. Inhibitors,Modulators,Libraries In our experiments, both cell lines expressed different HDACs and responded similarly to the treatment with vorinostat. That might make endometrial stromal sarcomas and uterine sarcomas in general potential candidates for treatment with vorino stat and/or other HDAC inhibitors. Both our in vitro and in vivo data clearly indicate Inhibitors,Modulators,Libraries that vorinostat is able to significantly reduce MES SA cell growth already after a short treatment period and at a dose range used thera peutically in the clinic.
Moreover, it has been shown by others that in this concentration range vorinostat is well tolerated and causes Inhibitors,Modulators,Libraries only minor side effects in patients. In our experiments we did not observe any patho logical changes in the main organs in mice, suggesting Bioactive compound that vorinostat may have no pronounced toxic effects during treatment over 21 days. These data correlate well with data from long term studies in humans, in which vorinostat has been used as a therapeutic agent for cutaneous T cell lymphoma and some other solid tumors.
Related posts: