Abstract
Background: Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life. Methods: The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin–Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP–Curcumin (Au-C), AuNP–Paclitaxel (Au-P), and AuNP–Curcumin–Paclitaxel (Au-CP)) in various in vitro and in vivo models. Results: The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups. Conclusions: Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses.
Highlights
According to the published report by the International Agency for Research Cancer (IARC) on the global burden and the incidence of various cancer cases (36 types of cancers) in the year 2020 using a statistical database (i.e., Globocan 2020), around 19.3 million active cases and 10 million cancer-related deaths were reported in over 185 countries
After synthesis of drug conjugated gold nanoparticles, initially, we evaluated physicochemical parameters such as hydrodynamic diameter (HDD), zeta potentials, and polydispersity index (PDI) of Au-C, Au-P, and Au-CP by using dynamic light scattering spectroscopy (DLS) in various media (Mili-Q water and 10% serum containing media has a lot of BSA proteins, these proteins may bind to the surface of the gold nanoparticles and it may help to increase the surface diameter of the gold nanoparticles [21,22] (Table 1)
Observations in this study revealed that Cur, Pacli, CP, Au-C, Au-P, and Au-CP inhibited the metastasis of negative breast cancer cells by downregulating signal transducer and activator of transcription 3 (STAT3), MMP2/9, and cyclin D-1 and induced apoptosis in both in vitro and in vivo models and our findings co-relate with the literature [40–43]
Summary
According to the published report by the International Agency for Research Cancer (IARC) on the global burden and the incidence of various cancer cases (36 types of cancers) in the year 2020 using a statistical database (i.e., Globocan 2020), around 19.3 million active cases and 10 million cancer-related deaths were reported in over 185 countries Among these 19.3 million cases, the incidence of breast cancer cases was higher in comparison to other cancer cases [1]. Methods: The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin–Paclitaxel (CP), and in conjugation with gold nanoparticles The present study is well supported with observations from cell-based assays, molecular and histopathological analyses
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