Antiproliferative effects of NDC2 and its analogues against human hepatocellular carcinoma (HepG2) cell line

Abstract

Event Abstract Back to Event Antiproliferative effects of NDC2 and its analogues against human hepatocellular carcinoma (HepG2) cell line Sau Har Lee1*, Cheng Foh Le2 and Chu Xin Ng1 1 School of Biosciences, Taylor's University, Malaysia 2 University of Nottingham Malaysia Campus, Malaysia Background Liver cancer is the second most common cause of mortality from cancer worldwide, with a mortality to incidence ratio as high as 0.95. This is mainly attributed to multidrug resistance developed by liver cancer cells after exposure to conventional chemotherapies. Hence, development of therapeutic peptides as a new chemotherapeutic drug might be a promising approach. NDC2 is an Aurein 1.2-like antibacterial and antitumour peptide that was shown to display minimal cell toxicity. We selected this peptide as the template to design five synthetic analogues (ND1–ND5) to enhance its anticancer potential. Therefore, the purpose of this study is to evaluate the in vitro antiproliferative properties of NDC2 and its analogues against human hepatocellular carcinoma (HepG2) cell line. Methods Each ND analogue was introduced with multiple residual alterations at specific positions at the C-terminal arm. Its anticancer potentials were predicted using the AntiCP anticancer peptide prediction tool. Subsequently, MTT assay was carried out to investigate the potential cytotoxic properties of NDs against HepG2 cells, up to a concentration of 256μg/ml for 24, 48 and 72 hours. Results Based on AntiCP algorithm, an anticancer peptide should exhibit SVM score greater than 1.0. From our analysis, only ND1–ND4 showed SVM scores ranging from 1.43–1.78, indicating their higher potential as anticancer peptides. These findings were supported by MTT results that showed both ND5 and the template NDC2 do not possess antiproliferative activity against HepG2 cells. Contrarily, ND1–ND4 exhibited antiproliferative activity against HepG2 cells with IC50 values ranging from 54–104µg/mL after 24 hours treatment. Among these analogues, ND4 was found to be most potent against HepG2 cells, with IC50 value of 54.811±3.403µg/mL. Our findings also showed that there was no significant time-dependent effects for each ND on HepG2 cells. Conclusion The four ND1–ND4 analogues exhibited antiproliferative activity against HepG2 cells, thus could represent as promising candidates for treatment against liver cancer. Hence, the anticancer mechanisms of the ND analogues should be further studied. Keywords: Anticancer peptides (ACPs), Drug Discovery, liver cancer, HepG2, cancer therapy Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Cancer Citation: Lee S, Le C and Ng C (2019). Antiproliferative effects of NDC2 and its analogues against human hepatocellular carcinoma (HepG2) cell line. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00148 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Sau Har Lee, School of Biosciences, Taylor's University, Subang Jaya, Selangor Darul Ehsan, 47500, Malaysia, sauhar.lee@taylors.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sau Har Lee Cheng Foh Le Chu Xin Ng Google Sau Har Lee Cheng Foh Le Chu Xin Ng Google Scholar Sau Har Lee Cheng Foh Le Chu Xin Ng PubMed Sau Har Lee Cheng Foh Le Chu Xin Ng Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.