Abstract
ObjectivesWe investigated the anti‐cancer activity of pentamidine, an anti‐protozoal cationic aromatic diamidine drug, in prostate cancer cells and aimed to provide valuable insights for improving the efficacy of prostate cancer treatment.Materials and methodsProstate cancer cell lines and epithelial RWPE‐1 cells were used in the study. Cell viability, wound‐healing, transwell and apoptosis assays were examined to evaluate the influences of pentamidine in vitro. RNA‐seq and qPCR were performed to analyse changes in gene transcription levels upon pentamidine treatment. Mitochondrial changes were assessed by measuring mitochondrial DNA content, morphology, membrane potential, cellular glucose uptake, ATP production and ROS generation. Nude mouse xenograft models were used to test anti‐tumour effects of pentamidine in vivo.ResultsPentamidine exerted profound inhibitory effects on proliferation, colony formation, migration and invasion of prostate cancer cells. In addition, the drug suppressed growth of xenograft tumours without exhibiting any obvious toxicity in nude mice. Mechanistically, pentamidine caused mitochondrial DNA content reduction and induced mitochondrial morphological changes, mitochondrial membrane potential dissipation, ATP level reduction, ROS production elevation and apoptosis in prostate cancer cells.ConclusionsPentamidine can efficiently suppress prostate cancer progression and may serve as a novel mitochondria‐targeted therapeutic agent for prostate cancer.
Highlights
According to 2018 global cancer statistics, prostate cancer is one of the most common cancers and a major cause of cancer‐related mortality in men worldwide.[1]
We investigated the anti‐cancer activity of an anti‐protozoal aromatic diamidine derivative, pentamidine, in prostate cancer cells
We further demonstrate that pentamidine causes mitochondrial DNA (mtDNA) reduction and induces mitochondrial morphological changes, mitochondrial dysfunction, Reactive oxygen species (ROS) generation and apoptosis in prostate cancer cells
Summary
According to 2018 global cancer statistics, prostate cancer is one of the most common cancers and a major cause of cancer‐related mortality in men worldwide.[1]. Pentamidine, a cationic aromatic diamidine drug, has been used clinically for the treatment of African trypanosomiasis, antimonial‐ resistant leishmaniasis and babesiosis as well as the prophylaxis of pneumocystis carinii pneumonia in acquired immune deficiency syn‐ drome (AIDS) patients for several decades.[19,20,21,22,23] While how the med‐ ication works is not entirely clear, it was found to rapidly localize to mitochondria and trigger disruption of mitochondrial membrane po‐ tential (ΔΨm) in parasite cells.[24,25,26] In addition, pentamidine can bind and strongly in the DNA minor groove at AT sequences and induce destruction in mtDNA of parasite kinetoplasts, which causes cell death.[27,28,29] In recent years, using pentamidine as an anti‐tumour drug has been proposed,[30,31,32,33,34] effects of pentamidine on prostate cancer are still poorly studied. Pentamidine causes mtDNA reduction, mitochon‐ drial morphological changes and dysfunction, which may serve as its anti‐tumour underlying mechanism
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
