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

Abstract

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.

Chrysophanol exhibits inhibitory activities against colorectal cancer by targeting decorin

“…In addition, it promoted caspase‐9 but not caspase‐8 activation, along with MMP loss and mitochondrial cytochrome C release into the cytosol, all of which indicated that chrysophanol induced apoptosis in CRC cells via the intrinsic pathway only. Our findings are consistent with previous studies showing that the pro‐apoptotic effects of chrysophanol in cancer cells correlated with decreased MMP . Altogether, mitochondrial dysfunction plays a key role in chrysophanol‐induced apoptosis.…”

Chrysophanol Suppresses Hypoxia‐Induced Epithelial‐Mesenchymal Transition in Colorectal Cancer Cells

“…However, it has been reported that the activation of PI3K/Akt signaling pathway could increase the HIF‐1α protein level without altering the HIF‐1α mRNA level (Laughner et al, ). In previous studies, chrysophanol has been shown to inactivate the PI3k/Akt signaling pathway in human prostate cancer and choriocarcinoma (Lim et al, ; Lu et al, ). Thus, we proposed that chrysophanol might modulate HIF‐1α expression via targeting the PI3k/Akt signaling pathway.…”

Chrysophanol attenuated isoproterenol‐induced cardiac hypertrophy by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

“…It possesses multiple biological activities, such as anti-oxidant, antimicrobial, and anti-inflammatory properties (Chu et al, 2018;Jeong et al, 2018). Previous researches have shown that chrysophanol can induce apoptosis and cell cycle arrest in diverse cancer cell lines (Lu et al, 2017;Ren et al, 2018). It was also reported to exert neuroprotection in animals suffering ischemia/reperfusion injury .…”