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• W2909609002 abstract "Event Abstract Back to Event Semisynthetic derivatives of andrographolide inhibit growth of pancreatic cancer cells via induction of G1 phase cell cycle arrest and apoptosis Sopna Devi Revindran1 and Johnson Stanslas1* 1 Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia Background Pancreatic ductal adenocarcinoma, is currently the fourth leading cause of cancer death globally due to poor prognosis and late diagnosis. Mutation of Kirsten-Ras (K-Ras) oncogene is prevalent in pancreatic cancer patient as more than 90% of patients inherit it. Andrographolide (AGP) and its benzylidene derivatives were found to bind to K-Ras transient pockets resulting in inhibition of K-Ras-MAPK oncogenic signaling. In the current investigation, growth inhibition, cell cycle arrest and apoptosis inducing potential of semisynthetic benzylidene derivatives of AGP, namely 3,19-(2-bromobenzylidene) andrographolide (SRJ09), 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) and 3,19-(2-bromobenzylidene)-14-acetylandrographolide (SRS07) were evaluated in Capan-2 (K-Ras G12V mutation) and PANC-1 (K-Ras G12D mutation) pancreatic cancer cell lines. Methods In vitro cytotoxic activity of AGP derivatives was assessed at 96 hours using MTT cell viability assay. Non-treated and treated cells were fixed in 70% ethanol and stained with propidium iodide before being subjected to quantification of cellular DNA content at different cell cycle stages by BD FACSCANTO II. Annexin V in combination with 7-Aminoactinomycin D (7-AAD) dye were used to stain cells, followed by analysis using Muse Cell Analyser that utilise fluorescent detection to detect phosphatidylserine (PS) on the surface of apoptotic cells. Results All three AGP derivatives were equally potent in Capan-2 and PANC-1 cells with IC50 values ranging from 3.2 µM to 4.9 µM. Cell cycle analysis showed that AGP analogue induced cell cycle arrest in G1 phase. Apoptosis assay revealed a decrease in viable cells, with concomitant increase in early and late apoptotic cells within 48 hours of exposure to AGP analogue. Conclusion The benzylidene derivatives of AGP inhibited growth of pancreatic cancer cells by inducing G1 phase cell cycle arrest and apoptosis. Keywords: Cell Cycle, Apoptosis, MTT assay, Pancreatic Cancer, andrographolide 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: Poster Presentation Topic: Cancer Citation: Revindran S and Stanslas J (2019). Semisynthetic derivatives of andrographolide inhibit growth of pancreatic cancer cells via induction of G1 phase cell cycle arrest and apoptosis. 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.2018.63.00127 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: 30 Sep 2018; Published Online: 17 Jan 2019. * Correspondence: Prof. Johnson Stanslas, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia, rcxjs@upm.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 Sopna Devi Revindran Johnson Stanslas Google Sopna Devi Revindran Johnson Stanslas Google Scholar Sopna Devi Revindran Johnson Stanslas PubMed Sopna Devi Revindran Johnson Stanslas 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." @default.
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• W2909609002 title "Semisynthetic derivatives of andrographolide inhibit growth of pancreatic cancer cells via induction of G1 phase cell cycle arrest and apoptosis" @default.
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