Co-delivery with nano-quercetin enhances doxorubicin-mediated cytotoxicity against MCF-7 cells

Abstract

Quercetin, the plant-derived phenolic compounds, plays a pivotal role in controlling hemostasis, by having potent antioxidant and free-radical scavenging properties. This flavonoid in combination with chemotherapeutic drugs improves the efficacy of these agents in induction of apoptosis in cancer cells. This study investigated the role of nano-quercetin (phytosome) in doxorubicin-induced apoptosis. Nanoparticles were characterized for particle size, zeta potential, scanning electron microscopy (SEM) and differential scanning calorimetric assessments. Anti-proliferative effect of formulations was evaluated by MTT assay. mRNA expression levels of target genes were measured by real time RT-PCR. The mean size of nanoparticles was 85 ± 2 nm with nearly narrow size distribution which was confirmed by SEM analysis. Our results showed that co-treatment of MCF-7 breast cancer cells with nano-quercetin and doxorubicin increased the percentage of apoptosis from 40.11 ± 7.72-58 ± 7.13 (p < 0.05). Furthermore, mRNA expression levels for downstream genes including NQO1 and MRP1 showed a marked decrease (p < 0.05). Taken together, our results suggest that phytosome technology can elevate the efficacy of chemotherapeutics by increasing the permeability of tumor cells to chemical agents. Our findings introduce a novel phytosome-dependent strategy to improve delivery of doxorubicin to the breast cancerous tissues.

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

“…Quercetin enhanced the antitumor effect of doxorubicin in HT29 colorectal cancer cell line [19], MCF-7 breast cancer cell line [20], liver cancer cells [21], and K562 human leukemia cell line [22]. Quercetin also showed cardioprotection against cardiotoxicity induced by doxorubicin [23, 24].…”

The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells

“…NQO1 and HO-1 are two major downstream targets of Nrf2, and serve a pivotal role in the maintenance of cellular redox homeostasis, thus preventing the transformation of normal cells to precancerous or malignant ones by counteracting ROS-mediated carcinogenesis (40). However, it was demonstrated that NQO1, in parallel with Nrf2 overexpression, aberrantly elevated the levels of HO1 in different types of cancer (40,41). Minaei et al demonstrated the effectiveness of nano-Qin decreasing the levels of NQO1 and multidrug resistance-associated protein 1without altering Nrf2 expression (41).…”

Dermal delivery of doxorubicin-loaded solid lipid nanoparticles for the treatment of skin cancer

“…Then, cells were replaced with 200 ll fresh media containing 20 ll of MTT solution (2 mg/ml) and incubated for 4 h at 37 C. Then, media was removed and 200 ll of DMSO and 25 ml of Sorenson-glycine buffer were added to dissolve the Formazon crystals. Finally, the absorbance at 570 nm after shaking for 15 min was measured using a microplate reader (Biotek, Winooski, VT) (Sharifi et al, 2015;Minaei et al, 2016).…”