Cargando…
Proscillaridin A induces apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in prostate cancer cells
Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer ac...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036078/ https://www.ncbi.nlm.nih.gov/pubmed/30008594 http://dx.doi.org/10.7150/ijms.23270 |
Sumario: | Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSN-A in various cancers including prostate cancer remain largely unexplored. In the present study, we have shown that PSN-A inhibits proliferation and induces apoptosis in prostate cancer cells in a dose-dependent manner. Further mechanistic study have shown that anticancer activity of PSN-A in prostate cancer cells is associated with ROS generation, Bcl-2 family proteins modulation, mitochondrial membrane potential disruption and ultimately activation of caspase-3 and cleavage of PARP. Moreover, we found that PSN-A inhibits JAK2/STAT3 signaling and augments doxorubicin toxicity in prostate cancer cells. Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer. |
---|