Cancer burden as a worldwide health issue arises from its increasing incidence together with depletion of efficacious treatment modalities. The current available treatments for cancer are surgery, radiotherapy and chemotherapy. The pharmaceutical industry is adopting a new paradigm shift towards a newer class of peptide-based drug that is expected to overcome the drawbacks of the conventional cancer therapeutics by offering more selectivity, easier synthesis, a wider safety profile and a lower cost of manufacture. The interest in peptides as anticancer agents began in the last few decades owing to their intrinsic properties, such as cationicity and small size, enabling them to compete as an efficacious anticancer agent.
In this study, we used data from the publicly available databases of anticancer peptides (ACPs) and the Red Sea metganomic database, created during AUC/KAUST Red Sea microbiome project. The project was done in two phases; in silico analysis followed by in vitro validation of the computational results. In silico analysis of our metagenome database resulted in a set of peptide hits that share similar composition to ACPs. One potential ACP hit was submitted for further computational prediction of its structure and function. Then, its sequence was chemically synthesized for subsequent in vitro functional assessment through cytotoxicity (MTT) assay, apoptosis/necrosis detection assay (Annexin/PI assay) and RNA expression analysis of Caspase 3. We used HepG2, U2OS, MCF7 and Hela as model cancer cell lines for testing its cytotoxicity.
The peptide showed evident, yet variable, dose dependent cytotoxicity in all tested cell lines. Membranolysis and Apoptosis could be concluded as possible mechanisms of action from the results of annexin assay and RT-PCR.
Our results, despite being consistent and in line with each other, more investigative techniques should be done for elucidation of the molecular mechanism of action of our anticancer peptide lead.
American University in Cairo
American University in Cairo
All authors have declared no conflicts of interest.