OBJECTIVE Prostate cancer is one of the most commonly diagnosed cancers worldwide.Current therapies for metastatic prostate cancer are only marginally effective,and hence novel treatment modalities are urgently needed...OBJECTIVE Prostate cancer is one of the most commonly diagnosed cancers worldwide.Current therapies for metastatic prostate cancer are only marginally effective,and hence novel treatment modalities are urgently needed.Considerable evidence suggests that chronic inflammation plays a pivotal role in the development and progression of prostate cancer.Thus agents that can suppress these inflammatory mediators could form the basis of novel therapy for prostate cancer patients.In our study,we focused on analyzing the potential anticancer effects of nimbolide,a terpenoid lactone derived from Azadirachta indica(Neem tree)against prostate cancer.METHODS Molecular biology techniques such as western blot analysis,DNA binding,luciferase assays,and immunohistochemistry were used for both in vitro and in vivo experiments.RESULTS Data from the in vitrostudies indicated that nimbolide could inhibit cell proliferation,induce apoptosis and suppress cellular invasion and migration.Interestingly,nimbolide also abrogated the activation of pro-inflammatory STAT 3 transcription factor,and this effect was found to be mediated via an increased production of reactive oxygen species(ROS),whereas depletion of ROS attenuated pSTAT 3 inhibitory effects of the drug.The in vivo efficacy of nimbolide was also noted in transgenic adenocarcinoma of mouse prostate(TRAMP)model,in which this triterpenoid significantly suppressed the tumor progression and growth without exhibiting any substantial adverse effects.CONCLUSION Overall our findings indicate that nimbolide exhibits significant anticancer effects in prostate cancer,and these effects may be mediated at least in part through the modulation of STAT 3 signaling pathway.展开更多
基金The project supported by agrant from NUS Academic Research Fund
文摘OBJECTIVE Prostate cancer is one of the most commonly diagnosed cancers worldwide.Current therapies for metastatic prostate cancer are only marginally effective,and hence novel treatment modalities are urgently needed.Considerable evidence suggests that chronic inflammation plays a pivotal role in the development and progression of prostate cancer.Thus agents that can suppress these inflammatory mediators could form the basis of novel therapy for prostate cancer patients.In our study,we focused on analyzing the potential anticancer effects of nimbolide,a terpenoid lactone derived from Azadirachta indica(Neem tree)against prostate cancer.METHODS Molecular biology techniques such as western blot analysis,DNA binding,luciferase assays,and immunohistochemistry were used for both in vitro and in vivo experiments.RESULTS Data from the in vitrostudies indicated that nimbolide could inhibit cell proliferation,induce apoptosis and suppress cellular invasion and migration.Interestingly,nimbolide also abrogated the activation of pro-inflammatory STAT 3 transcription factor,and this effect was found to be mediated via an increased production of reactive oxygen species(ROS),whereas depletion of ROS attenuated pSTAT 3 inhibitory effects of the drug.The in vivo efficacy of nimbolide was also noted in transgenic adenocarcinoma of mouse prostate(TRAMP)model,in which this triterpenoid significantly suppressed the tumor progression and growth without exhibiting any substantial adverse effects.CONCLUSION Overall our findings indicate that nimbolide exhibits significant anticancer effects in prostate cancer,and these effects may be mediated at least in part through the modulation of STAT 3 signaling pathway.
