Evaluation of the protective effect of curcumin nanoparticles on lung cells (Beas-2B) treated with paclitaxel nanoparticles: targeting oxidative stress

Paclitaxel (PTX) remains one of the most widely used chemotherapeutic agents in cancer therapy although it is associated with severe side effects. Therefore, the combination therapy with curcumin (CUR) is anticipated to decrease the toxicities of PTX towards healthy cells and enhance anti-cancer activities simultaneously. However, both PTX and CUR have low aqueous solubility. Therefore, this study evaluates the efficacy of CUR-nanoparticles (CUR-NPs) in reducing the toxicity of PTX nanoparticles (PTX-NPs) towards normal lung cells (Beas-2B). The PVA-coated CUR-NPs and PTX-NPs were subjected to physical and chemical stability evaluation by measuring for particle size, polydispersity (PDI) using dynamic light scattering (DLS), and drug content in media (with and without serum) as well as in phosphate buffer saline (PBS) using high performance liquid chromatography (HPLC). The MTS cytotoxicity data revealed that the incorporation of CUR-NPs with the PTX-NPs formulation effectively reduced the toxicity effect of PTX. This protective effect further resulted in the reduction of caspase-3, cytochrome C, reactive oxygen species (ROS), and apoptotic levels on Beas-2B. PTX-NPs exerts its toxicity towards Beas-2B via oxidative-stress related events. Higher levels of intracellular ROS have led to higher expression of NFκB and lipid peroxidation. When cells were pretreated with ROS inhibitor (N-acetyl-L-cysteine, NAC, 1mM), the activities of the antioxidant enzymes (superoxide dismutase and glutathione) were enhanced which in turn resulted in the decrease in lipid peroxidation, NFκB activation, and inflammatory cytokine levels. In conclusion, the combination of CUR-NPs with PTX-NPs could potentially reduce the toxicity effect of PTX by modulating the level of ROS in Beas-2B, minimizing the level of oxidative stress.