Novel walnut peptide–selenium hybrids with enhanced anticancer synergism: facile synthesis and mechanistic investigation of anticancer activity

Abstract

This contribution reports a facile synthesis of degreased walnut peptides (WP1)-functionalized selenium nanoparticles (SeNPs) hybrids with enhanced anticancer activity and a detailed mechanistic evaluation of its superior anticancer activity. Structural and chemical characterizations proved that SeNPs are effectively capped with WP1 via physical absorption, resulting in a stable hybrid structure with an average diameter of 89.22 nm. A panel of selected human cancer cell lines demonstrated high susceptibility toward WP1-SeNPs and displayed significantly reduced proliferative behavior. The as-synthesized WP1-SeNPs exhibited excellent selectivity between cancer cells and normal cells. The targeted induction of apoptosis in human breast adenocarcinoma cells (MCF-7) was confirmed by the accumulation of arrested S-phase cells, nuclear condensation, and DNA breakage. Careful investigations revealed that an extrinsic apoptotic pathway can be attributed to the cell apoptosis and the same was confirmed by activation of the Fas-associated with death domain protein and caspases 3, 8, and 9. In addition, it was also understood that intrinsic apoptotic pathways including reactive oxygen species generation, as well as the reduction in mitochondrial membrane potential, are also involved in the WP1-SeNP-induced apoptosis. This suggested the involvement of multiple apoptosis pathways in the anticancer activity. Our results indicated that WP1-SeNP hybrids with Se core encapsulated in a WP1 shell could be a highly effective method to achieve anticancer synergism. Moreover, the great potential exhibited by WP1-SeNPs could make them an ideal candidate as a chemotherapeutic agent for human cancers, especially for breast cancer.

Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway

“…Cell viability was evaluated using MTT assays [ 45 ]. The cells were seeded in 96-well plates at a density of 4,000 cells per well and then treated with geridonin, paclitaxel, or oridonin.…”

“…The mitochondrial membrane potential was measured using JC-1 dye [ 45 , 47 ]. MGC 803 cells were seeded on glass coverslips and treated with geridonin, paclitaxel, or geridonin plus paclitaxel for 24 h. MGC 803 cells were then stained with 5 μg/mL JC-1 (Beyotime Biotechnology) at 37°C for 20 min.…”

Small Molecule Oligopeptides Isolated from Walnut (Juglans regia L.) and Their Anti-Fatigue Effects in Mice

“…Walnut has extensive health-promoting functions, including antifungal [14], antitumor [14], antioxidant [13], anti-inflammatory [15], immune modulation [14], and antihypertensive properties [16]. Bioactive peptides are important protein fragments that have a wide range of pharmacological functions, such as anti-oxidative, anti-hypoxia, antimicrobial and immunomodulatory [17]. One animal study showed that oral administration of walnut extract had anti-fatigue effects and could significantly elevate exercise tolerance in mice [18].…”

Bioactive peptides from nuts: A review

“…(2016) who developed a method for the synthesis of walnut peptide (WP1)‐functionalized selenium nanoparticles (SeNPs) as an anticancer system. This delivery system improved peptide stability and increased the anticancer activity of SeNPs (Ren et al ., 2016).…”