The Potential Therapeutic Role of Green-Synthesized Selenium Nanoparticles Using Carvacrol in Human Breast Cancer MCF-7 Cells

Abstract

The disadvantages and side effects of currently available breast cancer (BC) therapies have compelled researchers to seek new therapeutic strategies. This study was designed to investigate the effect of selenium nanoparticles biosynthesized with carvacrol (SeNPs-CV) on breast cancer (MCF-7) cell lines and to explore possible underlying pathways. Flow cytometry, MTT assays, and various biochemical techniques were used to evaluate the anti-proliferative effects of SeNPs-CV on MCF-7 cells. Cytotoxicity assays showed that treatment with SeNPs-CV could effectively reduce MCF-7 cell proliferation and viability in a dose-dependent manner. However, SeNPs-CV had no cytotoxic effect against Vero cells. Furthermore, SeNPs-CV showed better anticancer activity than metal nanoparticles of selenium evidenced by the lower IC50 obtained in MCF-7 cells (8.3 µg/mL versus 41.6 µg/mL, respectively). Treatment with SeNPs-CV directly targeted Bcl-2, Bax, and caspase-3, leading to the mitochondrial leakage of cytochrome C and subsequent activation of the apoptotic cascade in MCF-7 cells. In addition, MCF-7 cells treated with SeNPs-CV exhibited elevated levels of oxidative stress, as indicated by noticeable rises in 8-OHDG, ROS, NO, and LPO, paralleled by significant exhaustion in GSH levels and antioxidant enzymes activity. In addition, the administration of SeNPs-CV induced the inflammatory mediator IL-1β and downregulated the expression of cell-proliferating nuclear antigen (PCNA) in MCF-7 cells, which plays a critical role in apoptosis. Therefore, the ability of SeNPs-CV to fight BC may be due to its ability to induce oxidative stress, inflammation, and apoptosis in tumor cells. These findings demonstrate the therapeutic potential of Se nanoparticles conjugated with CV, which may provide a novel approach for combination chemotherapy in BC.

Facile green synthesis and characterization of Terminalia arjuna bark phenolic–selenium nanogel: a biocompatible and green nano-biomaterial for multifaceted biological applications

“…Consistent with some prior investigations, SeNPs were found to inhibit cell migration. Moreover, the study results are in line with those of previous studies that have confirmed the antimigration effect on SeNPs in several different types of cancer cell lines ( Othman et al, 2023 ). Additionally, previous investigations demonstrated that SeNPs dramatically attenuate apoptosis in several cancer cell lines, with MDA-MB-231 cells being the most susceptible and MCF-7 cells being the least sensitive, suggesting that the efficacy of SeNPs may vary depending on the type of cancer cells ( Li et al, 2021 ).…”

Selenium Nanoparticles: Green Synthesis and Biomedical Application

“…Thus, an increase in the activity of caspase-3, the most important signaling module of the apoptosis cascade that plays a vital role in protein breakdown, provokes the programmed destruction of lung cancer cells, as was demonstrated for E. coli-mediated SeNPs [209]. Treatment with Carvacrol-mediated SeNPs directly targeted Bcl-2, Bax, and caspase-3, leading to the mitochondrial leakage of cytochrome C and subsequent activation of the apoptotic cascade in MCF-7 cells [151]. SeNPs dose-dependently increased caspase-3 levels in cancer cells; moreover, in normal cells, the SeNP concentration necessary to induce an increase in the caspase-3 level was found to be significantly higher compared to RAW 264.7, Caco-2, MCF-7, and IMR-32 cancer cells [130].…”

“…The significant induction of oxidative stress markers, such as ROS, 8-OHDG, LPO, and NO, was accompanied by a decrease in antioxidant marker levels (CAT, SOD, GPx activity and GSH levels) in MCF-7 cells exposed to green SeNPs, in contrast to control cells [151]. Possessing antioxidant properties, GSH not only protects the cell from toxic free radicals, but also generally determines the redox characteristics of the intracellular environment.…”

“…Such examples include SeNP synthesis using berberine, a plant alkaloid with anticancer and antisclerotic effects [147]; apigenin is one of the most common aglycones of flavones, a natural antioxidant with anti-inflammatory and anticarcinogenic properties [148]; bee propolis, known for many centuries for its antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, and cardioprotective properties, can synthesize nanoparticles due to its broad range of biomolecules like phenols, flavonoids, alkaloids, steroids, terpenoids, etc. [149]; by bioactive compounds of honey [150]; by Carvacrol-a member of the monoterpenoid phenols, possessing antimutagenic, analgesic, antimicrobial, antitumor, antiparasitic, and antioxidant activity [151]; by enzyme synthesis using bovine serum albumin as a reducing agent [152]; with naringenin and baicalin participation as capping agents-flavonoids with antimicrobial and antiinflammatory effects [153]-and zein (a class of prolamine proteins contained in corn) [154]. Such an abundance of approaches to biosynthesis and applied biological objects represent an inexhaustible storehouse of possibilities both for SeNP production and for further biomedical application.…”

“…The proliferating cell nuclear antigen (PCNA) is called the "ringmaster of the genome" because it regulates the cell cycle and participates in DNA synthesis, suggesting its active role in oncogenesis. Therefore, PCNA is widely used as a cell proliferation marker in both healthy and malignant tissues since it usually reflects cell proliferation activity [151]. Interestingly, SeNPs reduced the PCNA expression level in MCF-7 cells, showing their role in suppressing oncogenesis and proliferation in breast cancer by inhibiting PCNA gene expression [151].…”