In silico identification and in vitro assessment of a potential anticancer peptide sequence retrieved from the Red sea metagenomics library

Abstract

IC50 values of 0.98 lg/mL, 1.45 lg/mL, 8.02 lg/mL and 12.57 lg/mL in CCRF-CEM cells. They were further tested in 8 other cell lines as well as in normal AML12 hepato-cytes. IC50 values ranging from 2.71 lg/mL (towards glioblastoma U87MG.DEGFR cells) to 10.30 lg/mL (towards breast adenocarcinoma MDA-MB-231-BCRP cells) for AAB, from 3.43 lg/mL (towards U87MG cells) to 10.77 lg/mL (towards colon carcin-oma HCT116 (p53À/À) cells) for AAR and from 0.11 lg/mL (towards CCRF-CEM cells) to 108 lg/mL (towards leukemia CEM/ADR5000 cells) for doxorubicin (as con-trol drug) were obtained. ACL and ACB extracts displayed selective activities. AAR and ACL extracts induced apoptosis in CCRF-CEM cells, through caspases activation and loss of MMP, while apoptotic cell death was mediated by MMP diruption and increase ROS production for ACL. Conclusions: Some of the tested plants namely Albizia adianthifolia, Alchornea cordi-folia, Alchornea laxiflora, Pennisetum purpureum, Spathodea campanulata represent a potential source of novel anticancer drugs. Especially, Albizia adianthifolia and Alchornea cordifolia revealed considerable cytotoxic activities that could be exploited to develop phytomedicines to fight cancers including MDR phenotypes. Legal entity responsible for the study: Ministry of Scientific Research and Innovation (MINRESI) University of Yaounde I Funding: Has not received any funding Disclosure: The author has declared no conflicts of interest. 91P Novel effect of acetyl-11-keto-boswellic acid (AKBA) on mitophagy-induced apoptosis using cellular proteomic profiling Background: Terpenoids and their potential analogues have attracted recent attention to their anti-cancer activity with lower adverse effects. Acetyl-11-keto-boswellic acid (AKBA) is a derivative of boswellic acid that exerts anti-cancer properties against differ-ent types of cancer cells. AKBA is known to induce apoptosis via activation of caspase 8 and also induction of epigenetic pathways via regulation of histone deacetylase gene ex-pression. However, molecular targets and pathways are not identified. In this study we implemented in-depth non-labelled proteomic profiling of MCF-7 breast cancer cells treated with AKBA. Methods: Breast cancer cell line MCF7 was treated at IC50 dose of AKBA. Protein lys-ates from treated and untreated cell lines were purified and digested with trypsin. Isolated peptides were subjected to non-labelled proteomic profiling using Orbitrap lC-MS using service facility. Proteomic signal ratios were normalized using variance stabilizing normalization and corrected for false detection ratio. Results: A total of 137 proteins were significantly up-regulated or downregulated. A set of mitochondrial proteins were downregulated and set of autophagy pathway proteins were up-regulated. Further confirmation of mitophagy pathway was studied using western blot of the SQTRM, PLINK, and PINK-1 proteins. Similarly, mitochondrial contents were measured to confirm mitochondrial degradation. To assess if mitochon-drial loss is due to the autophagy pathway, we performed dual staining for LC3 and mitochondrial markers. Conclusions: Our results show for first time that AKBA induced apoptosis via mitoph-agy pathway which explains previously known AKBA induction of caspase-8 pathway. AKBA provides a novel therapeutic agent that is capable of induction of apoptosis in cancer cells with less toxicity to normal cells.