Gold-chrysophanol nanoparticles suppress human prostate cancer progression through inactivating AKT expression and inducing apoptosis and ROS generation in vitro and in vivo

• DOI: 10.3892/ijo.2017.4095
• Publication Date: 2017-08-10T12:22:50Z
• Authors: Li Lu; Ke Li; Yun-Hua Mao; Hu Qu; Bing Yao; Wen-Wen Zhong; Bo Ma; Zhong-Yang Wang
• Keywords: Male; 0301 basic medicine; Metal Nanoparticles; Mice, Nude; Prostatic Neoplasms; Anthraquinones; Apoptosis; Articles; Xenograft Model Antitumor Assays; 3. Good health; Enzyme Activation; Mice, Inbred C57BL; Mice; Random Allocation; 03 medical and health sciences; Cell Line, Tumor; Disease Progression; Animals; Humans; Female; Gold; Reactive Oxygen Species; Proto-Oncogene Proteins c-akt

Controlled releasing of regulations remains the most convenient method to deliver various drugs. In the present study, we precipitated gold nanoparticles with chrysophanol. The gold-chrysophanol into poly (DL-lactide-co-glycolide) nanoparticles was loaded and the biological activity of chrysophanol nanoparticles on human LNCap prostate cancer cells, was tested to acquire the sustained releasing property. The circular dichroism spectroscopy indicated that chrysophanol nanoparticles effectively resulted in conformational alterations in DNA and regulated different proteins associated with cell cycle arrest. The reactive oxygen species (ROS), apoptosis, cell cycle, DNA damage, Cyto-c and caspase-3 activity were analyzed, and the expression levels of different anti- and pro-apoptotic were studied using immunoblotting analysis. The cytotoxicity assay suggested that chrysophanol nanoparticles preferentially killed prostate cancer cells in comparison to the normal cells. Chrysophanol nanoparticles reduced histone deacetylases (HDACs) to suppress cell proliferation and induce apoptosis by arresting the cell cycle in sub-G phase. In addition, the cell cycle-related proteins, including p27, CHK1, cyclin D1, CDK1, p-AMP-activated protein kinase (AMPK) and p-protein kinase B (AKT), were regulated by chrysophanol nanoparticles to prevent human prostate cancer cell progression. Chrysophanol nanoparticles induced apoptosis in LNCap cells by promoting p53/ROS crosstalk to prevent proliferation. Pharmacokinetic study in mice indicated that chrysophanol nanoparticle injection showed high bioavailability compared to the free chrysophanol. Also, in vivo study revealed that chrysophanol nanoparticles obviously reduced tumor volume and weight. In conclusion, the data above suggested that chrysophanol nanoparticles might be effective to prevent human prostate cancer progression.