ABSTRACT
Introduction: The approach for drug delivery has impressively developed with the emergence of nanosuspension, particularly the targeted nanoemulsions (NEs). It can potentially improve the bioavailability of drugs, enhancing their therapeutic efficiency. This study aims to examine the potential role of NE as a delivery system for the combination of docetaxel (DTX), a microtubule-targeting agent, and thymoquinone (TQ) in the treatment of human ductal carcinoma cells T47D. Methods: NEs were synthesized by ultra-sonication and characterized physically by dynamic light scattering (DLS). A sulforhodamine B assay was performed to evaluate cytotoxicity, and a flow cytometry analysis for cell cycle, apoptosis, autophagy, and cancer stem cell evaluations. A quantitative polymerase chain reaction further assessed the epithelial-mesenchymal transition gene expirations of SNAIL-1, ZEB-1, and TWIST-1. Results: The optimal sizes of blank-NEs and NE-DTX+TQ were found at 117.3 ± 8 nm and 373 ± 6.8 nm, respectively. The synergistic effect of the NE-DTX+TQ formulation significantly inhibited the in vitro proliferation of T47D cells. It caused a significant increase in apoptosis, accompanied by the stimulation of autophagy. Moreover, this formulation arrested T47D cells at the G2/M phase, promoted the reduction of the breast cancer stem cell (BCSC) population, and repressed the expression of TWIST-1 and ZEB-1. Conclusion: Co-delivery of NE-DTX+TQ may probably inhibit the proliferation of T47D via the induction of apoptosis and autophagy pathways and impede the migration by reducing the BCSC population and downregulating TWIST-1 expression to decrease the epithelial-to-mesenchymal transition (EMT) of breast cancer cells. Therefore, the study suggests the NE-DTX+TQ formula as a potential approach to inhibit breast cancer growth and metastasis.
ABSTRACT
Combining more than one anticancer agent in a nanocarrier is beneficial in producing a formula with a low dose and limited adverse side effects. The current study aimed to formulate docetaxel (DTX) and thymoquinone (TQ) in borage oil-based nanoemulsion (B-NE) and evaluate its potential in impeding the growth of breast cancer cells. The formulated B-NE and the combination (DTX + TQ) B-NE were prepared by the ultra-sonication method and physically characterized by the dynamic light scattering techniques. The cytotoxicity analyses of (DTX + TQ) B-NE in MCF-7 and MDA-MB-231 cells were evaluated in vitro by using the SRB assay. Cell death mechanisms were investigated in terms of apoptosis and autophagy pathways by flow cytometry. The optimum mean droplet sizes formulated for blank B-NE and the (DTX + TQ) B-NE were 56.04 ± 4.00 nm and 235.00 ± 10.00 nm, respectively. The determined values of the half-maximal inhibitory concentration (IC50) of mixing one-half amounts of DTX and TQ in B-NE were 1.15 ± 0.097 µM and 0.47 ± 0.091 µM in MCF-7 and MDA-MB-231 cells, respectively, which were similar to the IC50 values of the full amount of free DTX in both tested cell lines. The treatment with (DTX + TQ) B-NE resulted in a synergistic effect on both tested cells. (DTX + TQ) B-NE induced apoptosis that was integrated with the stimulation of autophagy. The produced formulation enhances the DTX efficacy against human breast cancer cells by reducing its effective dose, and thus it could have the potential to minimize the associated toxicity.
