Algae-meditated route to cuprous oxide (Cu2O) nanoparticle: differential expression profile of MALAT1 and GAS5 LncRNAs and cytotoxic effect in human breast cancer

Abstract

Background Breast cancer (BC), as the most widely recognized disease in women worldwide, represents about 30% of all cancers impacting women. This study was aimed to synthesize Cu2O nanoparticles from the cystoseira myrica algae (CM-Cu2O NPs) assess their antimicrobial activity against pathogenic bacteria and fungi. We evaluated the expression levels of lncRNAs (MALAT1 and GAS5) and apoptosis genes (p53, p27, bax, bcl2 and caspase3), their prognostic roles. Methods In this study, CM-Cu2O NPs synthesized by cystoseira myrica algae extraction used to evaluate its cytotoxicity and apoptotic properties on MDA-MB-231, SKBR3 and T-47D BC cell lines compared to HDF control cell line. The CM-Cu2O NPs was characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM). The antimicrobial activity of CM-Cu2O NPs was assessed against pathogenic bacteria, staphylococcus aureus (S. aureus) PTCC 1112 bacteria as a standard gram-positive bacteria and pseudomonas aeruginosa (P. aeruginosa) PTCC 1310 as a standard gram-negative bacterium. Expression profile of MALAT1 and GAS5 lncRNAs and apoptosis genes, i.e., p27, bax, bcl2 and caspase3 genes, were calculated utilizing qRT-PCR. The changes in the expression levels were determined using the DDCT method. Results MALAT1 was upregulated in MDA-MB-231, SKBR3 and T-47D BC (p < 0.01), while GAS5 was downregulated in SKBR3 and T-47D cell lines tested compared with HDF control cell line (p < 0.05) was found. The results revealed that, p27, bax and caspase3 were significantly upregulated in BC cell lines as compared with normal cell line. Bcl2 expression was also significantly increased in MDA-MB-231 and T47D cell lines compared with normal cell line, but bcl2 levels were downregulated in SKBR3 cell line. Conclusions Our results confirm the beneficial cytotoxic effects of green-synthesized CM-Cu2O NPs on BC cell lines. This nanoparticle decreased angiogenesis and induces apoptosis, so we conclude that CM-Cu2O NPs can be used as a supplemental drug in cancer treatments. Significantly, elevated circulating lncRNAs were demonstrated to be BC specific and could differentiate BC cell lines from the normal cell lines. It was demonstrated that lncRNAs used in this study and their expression profiles can be created as biomarkers for early diagnosis and prognosis of BC. Further studies utilizing patients would give recognizable identification of lncRNAs as key players in intercellular interactions.

Evaluation of Anticancer Potential of Biogenic Copper Oxide Nanoparticles (CuO NPs) against Breast Cancer

“…It is wellknown that excessive generation of ROS/RNS, oxidative stress, and cancer cell Sub G1 arrest is connected to DNA damage and apoptosis/necrosis [41,42]. Our results agree with earlier studies that observed induction of apoptosis as a result of green synthesized nanoparticles [40,43]. Of late, endoplasmic reticulum stress-mediated induction of apopto-sis has also been reported in response to CuO NP treatment in Wistar rats [44].…”

“…Apoptosis is considered a significant anticancer mechanism that involves the activation of a sequence of molecular events culminating into cell death with cellular, 3 Journal of Nanomaterials morphological, and biochemical changes [40]. It is wellknown that excessive generation of ROS/RNS, oxidative stress, and cancer cell Sub G1 arrest is connected to DNA damage and apoptosis/necrosis [41,42].…”

Biogenic copper oxide nanoparticles from Bacillus coagulans induced reactive oxygen species generation and apoptotic and anti-metastatic activities in breast cancer cells

“…An in vitro study indicated that CuONPs treatment increased the expression of the P53 tumor suppressor gene, and an elevation in the BAX / BCL2 ratio revealed that a mitochondria-mediated mechanism is engaged in CuONPs-induced programmed cell death 17 . The findings of another investigation showed that the expression levels of P21 , BAX , and CASP3 were considerably elevated, and BCL2 dramatically declined in CuONPs-treated SKBR3 cells as compared to normal cells 83 .…”

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

“…Nanogels represent a versatile platform for drug delivery, with tunable properties. Clinical trials are necessary to assess their safety and effectiveness in different therapeutic contexts [ 162 , 163 ]. Cationic liposomes and chitosan nanoparticles offer unique advantages for gene and nucleic acid delivery.…”