The Combined Use of in Silico, in Vitro, and in Vivo Analyses to Assess Anti-cancerous Potential of a Bioactive Compound from Cyanobacterium Nostoc sp. MGL001

Abstract

Escalating incidences of cancer, especially in developed and developing countries, demand evaluation of potential unexplored natural drug resources. Here, anticancer potential of 9-Ethyliminomethyl-12-(morpholin-4-ylmethoxy)-5,8,13,16-tetraaza -hexacene-2,3-dicarboxylic acid (EMTAHDCA) isolated from fresh water cyanobacterium Nostoc sp. MGL001 was screened through in silico, in vitro, and in vivo studies. For in silico analysis, EMTAHDCA was selected as ligand and 11 cancer related proteins (Protein Data Bank ID: 1BIX, 1NOW, 1TE6, 2RCW, 2UVL, 2VCJ, 3CRY, 3HQU, 3NMQ, 5P21, and 4B7P) which are common targets of various anticancer drugs were selected as receptors. The results obtained from in silico analysis showed that EMTAHDCA has strong binding affinity for all the 11 target protein receptors. The ability of EMTAHDCA to bind active sites of cancer protein targets indicated that it is functionally similar to commercially available anticancer drugs. For assessing cellular metabolic activities, in vitro studies were performed by using calorimetric assay viz. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT). Results showed that EMTAHDCA induced significant cytotoxic response against Dalton's lymphoma ascites (DLA) cells in a dose and time dependent manner with an inhibitory concentration (IC50) value of 372.4 ng/mL after 24 h of incubation. However, in case of normal bone marrow cells, the EMTAHDCA did not induce cytotoxicity as the IC50 value was not obtained even with higher dose of 1,000 ng/mL EMTAHDCA. Further, in vivo studies revealed that the median life span/survival days of tumor bearing mice treated with EMTAHDCA increased significantly with a fold change of ~1.9 and 1.81 corresponding to doses of 5 and 10 mg/kg body weight (B.W.) of EMTAHDCA respectively, as compared to the DL group. Our results suggest that 5 mg/kg B.W. is effective since the dose of 10 mg/kg B.W. did not show any significant difference as compared to 5 mg/kg B.W. Taken together, our findings based on in silico, in vitro, and in vivo analyses suggest that EMTAHDCA has potential anticancer effects, and thus, can be considered for cancer treatment.

Research Progresses on the Physiological and Pharmacological Benefits of Microalgae-Derived Biomolecules

“…The extracts of water, dimethyl sulfoxide (DMSO), and acetone all inhibited the growth of Bacillus subtilis . Interestingly, the DMSO extract, but not the water or acetone extract, showed inhibitory effects on Klebsiella pneumoniae and Escherichia coli [ 50 ]. Levert A et al, identified three novel depsipeptides and thiosulfonamides from the French Polynesian marine cyanobacteria Lyngbya majuscula , which performed strong antimicrobial activity with the minimum inhibitory concentration of 6.7 μM [ 51 ].…”

Insight into the Potential Cyanobacterial Metabolites and their Screening Strategies

“…MGL001 has anticancer properties. It was found that cyanocompound EMTAHDCA induced significant cytotoxic response against Dalton's lymphoma ascites (DLA) cells with an inhibitory concentration (IC50) value of 372.4 ng/ mL in a dose and time dependent manner after 24 h of incubation 66 . Several marine cyanobacterial compounds interact with certain significant molecular targets which are involved in anticancer activity resulting in controlling the death of tumor cells, this targets to start the compounds to slow down the proliferation of cancer cells by inducing apoptotic cell death 67 .…”

“…These apoptotic cells develop complex structural alterations which allow the identification of tumor cells. During the early stages, cells become smaller in size, having dense cytoplasm with thin organelles in it 66 . Cell extracts from Cyanobium sp; CENA154, Nostoc spp; CENA64 & CENA 69, Oxynema sp; CENA135 have anticancer properties against murine colon cancer line CT-26 and lung cancer 3LL found in Brazilian cyanobacterial species 2 .…”

“…Secondary metabolites from the marine cyanobacterial species show great participation in producing effective drugs due to their unique structure frameworks and competency with significant biological activity such as antiinflammatory activity 23 . Chemically assorted compounds were found to induce the antiinflammatory activity 66 .…”

Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach

“…The available data can greatly help to design the new EGFR inhibitors from the diverse secondary metabolites associated with the plant and microbial sources. Apart from the plant derived compounds, the importance of secondary metabolites of microbes is reported in anticancer therapy using in vitro and in silico experiments [ 11 , 12 ].…”