AUTHOR=Alotaibi Badriyah S. , El-Masry Thanaa A. , Selim Hend , El-Bouseary Maisra M. , El-Sheekh Mostafa M. , Makhlof Mofida E. M. , El-Nagar Maysa M. F. 

TITLE=New insights into the anticancer effects of Polycladia crinita aqueous extract and its selenium nanoformulation against the solid Ehrlich carcinoma model in mice via VEGF, notch 1, NF-кB, cyclin D1, and caspase 3 signaling pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1345516

DOI=10.3389/fphar.2024.1345516

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Phaeophyceae species are enticing interest among researchers working in the nanotechnology discipline, because of their diverse biological activities such as anti-inflammatory, antioxidant, anti-microbial, and anti-tumor. In the present study, the anti-cancer properties of <italic>Polycladia crinita</italic> extract and green synthesized <italic>Polycladia crinita</italic> selenium nanoparticles (PCSeNPs) against breast cancer cell line (MDA-MB-231) and solid Ehrlich carcinoma (SEC) were investigated.</p><p><bold>Methods:</bold> Gas chromatography–mass spectroscopy examinations of <italic>Polycladia crinita</italic> were determined and various analytical procedures, such as SEM, TEM, EDX, and XRD, were employed to characterize the biosynthesized PCSeNPs. <italic>In vitro,</italic> the anticancer activity of free <italic>Polycladia crinita</italic> and PCSeNPs was evaluated using the viability assay against MDA-MB-231, and also cell cycle analysis by flow cytometry was determined. Furthermore, to study the possible mechanisms behind the <italic>in vivo</italic> anti-tumor action, mice bearing SEC were randomly allocated into six equal groups (n = 6). Group 1: Tumor control group, group 2: free SeNPs, group 3: 25 mg/kg <italic>Polycladia crinita</italic>, group 4: 50 mg/kg <italic>Polycladia crinita</italic>, group 5: 25 mg/kg PCSeNPs, group 6: 50 mg/kg PCSeNPs.</p><p><bold>Results:</bold> Gas chromatography–mass spectroscopy examinations of <italic>Polycladia crinita</italic> extract exposed the presence of many bioactive compounds, such as 4-Octadecenoic acid-methyl ester, Tetradecanoic acid, and n-Hexadecenoic acid. These compounds together with other compounds found, might work in concert to encourage the development of anti-tumor activities. <italic>Polycladia crinita</italic> extract and PCSeNPs were shown to inhibit cancer cell viability and early cell cycle arrest. Concentrations of 50 mg/kg of PCSeNPs showed suppression of COX-2, NF-кB, VEGF, ki-67, Notch 1, and Bcl-2 protein levels. Otherwise, showed amplification of the caspase 3, BAX, and P53 protein levels. Moreover, gene expression of caspase 3, caspase 9, Notch 1, cyclin D1, NF-кB, IL-6, and VEGF was significantly more effective with PCSeNPs than similar doses of free extract.</p><p><bold>Conclusion:</bold> The PCSeNPs mediated their promising anti-cancerous action by enhancing apoptosis and mitigating inflammation, which manifested in promoting the total survival rate and the tumor volume decrease.</p>