Curcumin-loaded nanoparticles enhance apoptotic cell death of U2OS human osteosarcoma cells through the Akt-Bad signaling pathway

Abstract

Curcumin has potential anticancer activity and has been shown to be involved in several signaling pathways including differentiation and apoptosis. Our previous study showed that water-soluble PLGA curcumin nanoparticles (Cur-NPs) triggered apoptotic cell death through regulation of the function of MDR1 and the production of reactive oxygen species (ROS) in cisplatin-resistant human oral cancer CAR cells. In this study, we investigated the anti-proliferative effects of Cur-NPs on human osteosarcoma U2OS cells. The morphology of Cur-NPs showed spherical shape by TEM analysis. The encapsulation efficiency of curcumin in Cur-NPs prepared by single emulsion was 90.5 ± 3.0%. Our results demonstrated that the curcumin fragments on the mass spectrum of Cur-NPs and the peaks of curcumin standard could be found on the Cur-NPs spectrum by 1H-NMR spectra analysis. Cur-NPs induced anti-proliferative effects and apoptosis in U2OS cells. Compared to the untreated U2OS cells, more detectable amount of Cur-NPs was found inside the treated U2OS cells. Cur-NPs induced DNA fragmentation and apoptotic bodies in U2OS cells. Both the activity and the expression levels of caspases-3/-7 and caspase-9 were elevated in the treated U2OS cells. Cur-NPs upregulated the protein expression levels of cleaved caspase-3/caspase-9, cytochrome c, Apaf-1 and Bad and downregulated the protein expression level of p-Akt in U2OS cells. These results suggest Cur-NPs are effective in enhancing apoptosis in human osteosarcoma cells and thus could provide potential for cancer therapeutics.

CCR9–CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway

“…In addition to influencing the expressions of apoptosis and anti-apoptosis genes, Akt can also promote cell survival through the direct phosphorylation of protein BAD [25,26]. AKT phosphorylates and inhibits BAD, thus preventing its binding and inhibition of Bcl-2 and Bcl-xl [27][28][29].…”

The effect of silver nanoparticles (AgNPs) on proliferation and apoptosis of in ovo cultured glioblastoma multiforme (GBM) cells

“…Since the majority of anticancer strategies initiate apoptosis through caspase 9 activation, the modulation of caspase 9 expression may be exploited by designing new ways to control apoptosis in malignant tumors, including GBM [39]. There are a lot of publications about the interactions between different types of nanoparticles and tumor cells which have shown that titanium dioxide nanoparticles as well as curcumin-loaded nanoparticles cause intrinsic-mediated apoptosis in human cells and that caspase 9 plays a critical role in this process [40,41]. However, none of these publications focused on the activation of caspase 9 in GBM.…”

Polyphenols delivery by polymeric materials: challenges in cancer treatment

“…The most of the proposed delivery nano-systems show mechanisms of action mirror that of free curcumin, allowing an effective passive targeting on different cancer cells, including cervical (Das et al, 2010), oral (Chang et al, 2013a), prostate (Mukerjee & Vishwanatha, 2009;Sanoj Rejinold et al, 2011), breast (Sanoj Rejinold et al, 2011 cancers, osteosarcoma (Peng et al, 2014), melanoma (Mangalathillam et al, 2012), and medulloblastoma (Altunbas et al, 2011) by controlling the CUR release over time. Furthermore, in vivo studies proved that nanoparticles prepared by free radical polymerization of N-isopropylacrylamide (NIPAAm), N-vinyl-2-pyrrolidone (VP), and poly(ethylene glycol) acrylate (PEG-mA), proposed for the treatment of pancreatic cancer, show negligible toxicity in mouse model (Bisht et al, 2007), while the emulsion polymerization of butyl-cyanoacrylate in the presence of CT allows the obtainment of a CUR delivery vehicles suitable for the treatment of hepatic cancer with favorable pharmacokinetic profiles (Duan et al, 2010).…”