RESUMEN
Natural bioactive compounds with antioxidant activity play remarkable roles in the prevention of reactive oxygen species (ROS) formation. ROS, which are formed by different pathways, have various pathological influences such as DNA damage, carcinogenesis, and cellular degeneration. Incremental demands have prompted the search for newer and alternative resources of natural bioactive compounds with antioxidant properties. The marine environment encompasses almost three-quarters of our planet and is home to many eukaryotic and prokaryotic microorganisms. Because of extreme physical and chemical conditions, the marine environment is a rich source of chemical and biological diversity, and marine microorganisms have high potential as a source of commercially interesting compounds with various pharmaceutical, nutraceutical, and cosmeceutical applications. Bacteria and microalgae are the most important producers of valuable molecules including antioxidant enzymes (such as superoxide dismutase and catalase) and antioxidant substances (such as carotenoids, exopolysaccharides, and bioactive peptides) with various valuable biological properties and applications. Here, we review the current knowledge of these bioactive compounds while highlighting their antioxidant properties, production yield, health-related benefits, and potential applications in various biological and industrial fields.
Asunto(s)
Antioxidantes/aislamiento & purificación , Bacterias/metabolismo , Microalgas/metabolismo , Antioxidantes/farmacología , Biotecnología/métodos , Carotenoides/aislamiento & purificación , Carotenoides/farmacología , Péptidos/aislamiento & purificación , Péptidos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
AIMS: Lipocalin 2 (Lcn2) is an antioxidant-related protein upregulated in various cellular stress conditions, especially cancer. In this study, we abrogated Lcn2 expression in MDA-MB-231 breast cancer cells using the CRISPR/Cas9 technology and evaluated its effect on cellular proliferation, migration, and ferroptotic cell death. MAIN METHODS: Validated human Lcn2 CRISPR/Cas9 knockout (KO) and homology-directed repair (HDR) plasmids were co-transfected into MDA-MB-231 breast cancer cells. Lcn2 gene knockout was confirmed at the transcriptional and protein levels using reverse transcription (RT)-PCR and enzyme-linked immunosorbent assay (ELISA). Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cytotoxicity assay was performed in the presence or absence of erastin, cisplatin (CDDP), and ferrostatin-1 using the CCK-8 method. Ferroptosis level was measured using the malondialdehyde assay lipid peroxidation kit. The migration capacity of the cells was also evaluated using the scratch assay. KEY FINDINGS: Targeting Lcn2 using CRISPR/Cas9 reduced cellular proliferation and migration capability, and elevated the vulnerability of MDA-MB-231 cells to cisplatin. Furthermore, Lcn2 expression loss effectively promoted erastin-mediated ferroptosis in MDA-MB-231 cells. SIGNIFICANCE: Inhibition of Lcn2 is a potentially useful strategy for sensitizing MDA-MB-231 tumor cells to ferroptotic cell death.
Asunto(s)
Neoplasias de la Mama , Ferroptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Sistemas CRISPR-Cas , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Femenino , Ferroptosis/genética , Humanos , Lipocalina 2/genética , PiperazinasRESUMEN
Nucleolin (NCL) is a multifunctional nucleolar phosphoprotein harboring critical roles in cells such as cell proliferation, survival, and growth. The dysregulation and overexpression of NCL are related to various pathologic and oncological indications. These characteristics of NCL make it an ideal target for the treatment of various cancers. AS1411 is a synthetic quadruplex-forming nuclease-resistant DNA oligonucleotide aptamer which shows a considerably high affinity for NCL, therefore, being capable of inducing growth inhibition in a variety of tumor cells. The high affinity and specificity of AS1411 towards NCL make it a suitable targeting tool, which can be used for the functionalization of therapeutic payloaddelivery nanosystems to selectively target tumor cells. This review explores the advances in NCL-targeting cancer therapy through AS1411-functionalized delivery nanosystems for the selective delivery of a broad spectrum of therapeutic agents.