Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma

Abstract

In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; *p < 0.05) while producing no or only minor toxicity in healthy cells (no toxicity at 100 μM; **p < 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF-1α, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over control; *p < 0.05). Overall, nano-therapeutic treatments showed a more pronounced effect in MYCN-amplified cells, which are traditionally more resistant to drug therapies. These results represent a very promising alternative to small molecule drug therapies for robust cancers.

Dose‐response assessment of chemically modified curcumin in experimental periodontitis

“…However, it is important to consider that these apparently contradictory findings may be related with the final concentration of CMC2.24 in vivo and within the macrophages in vitro. Other in vitro studies report contrasting effects of natural curcumin on production of ROS, depending on the cell type and concentration . In vivo, administration of natural curcumin has been shown to reduce oxidative stress by inhibiting NF‐kB signaling, which would also decrease the expression of various cytokines.…”

“…Other in vitro studies report contrasting effects of natural curcumin on production of ROS, depending on the cell type and concentration. [37][38][39][40][41][42] In vivo, administration of natural curcumin has been shown to reduce oxidative stress by inhibiting NF-kB signaling, 43 which would also decrease the expression of various cytokines. In fact, our research group has recently shown that CMC2.24 inhibits NF-kB signaling.…”

Nanoantioxidants: Recent Trends in Antioxidant Delivery Applications

“…CNPs have also been successfully used for the in vitro and in vivo treatment of different cancers, including neuroblastoma, the most recently focused one. However, the anti-cancer features of CNPs depend on the induction and accumulation of ROS with simultaneous decrease in antioxidant enzyme levels [61]. Curcumin possess anti-cancer properties, therefore, combination of CNPs and curcumin in one formulation may result in increased physiological activity.…”

Liposomes Aid Curcumin's Combat with Cancer in a Breast Tumor Model

“…International Publisher have been explored to encapsulate curcumin for treatment of various cancer types [16,17,[30][31][32].…”

“…CUR has biological and pharmacological relevance making it an exciting molecule with anti-inflammatory, anti-carcinogenic, anti-malarial and anti-viral properties, in addition to low toxicity [3,[6][7][8][9][10][11]. Efforts by others have shown the selectivity of CUR towards tumor cells compared to healthy cells which embarked the use of curcumin for cancer treatment [5,[12][13][14][15][16][17][18]. CUR has multiple anticancer facets including blocking tumor initiation, as well as suppressing tumor progression and inhibiting invasion and metastasis [8,12,[18][19][20][21][22][23].…”