Pentamidine inhibits prostate cancer progression via selectively inducing mitochondrial DNA depletion and dysfunction

• Published in: Cell proliferation 2020-01, Vol.53 (1), p.e12718-n/a
• Main Authors: Liu, Lin, Wang, Fan, Tong, Yu, Li, Lin‐Feng, Liu, Yanfeng, Gao, Wei‐Qiang
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Apoptosis; Biocompatibility; Biotechnology industry; Cell cycle; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell viability; Chemical compounds; Deoxyribonucleic acid; Depletion; DNA; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; Experiments; Gene expression; Humans; In vivo methods and tests; Male; Medical prognosis; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - genetics; Membranes; Mice; Mice, Nude; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial DNA; Morphology; Original; Parasitic diseases; PC-3 Cells; Pentamidine; Pentamidine - pharmacology; Pharmacology; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Reduction; Ribonucleic acid; RNA; Toxicity; Transcription; Tumor cell lines; Tumors; Wound healing; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12718

Objectives We 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 methods Prostate 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. Results Pentamidine 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. Conclusions Pentamidine can efficiently suppress prostate cancer progression and may serve as a novel mitochondria‐targeted therapeutic agent for prostate cancer.