Goniothalamin induces necroptosis and anoikis in human invasive breast cancer MDA-MB-231 cells

• Main Authors: Patompong Khaw-On, Wilart Pompimon, Ratana Banjerdpongchai
• Format: Journal
• Published: 2019
• Subjects: Biochemistry, Genetics and Molecular Biology; Chemical Engineering; Chemistry; Computer Science
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071497297&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/66585
• Institution: Chiang Mai University

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Goniothalamin (GTN) is toxic to several types of cancer cells in vitro. However, its effects on non-apoptotic cell death induction of human cancer cells have been poorly documented. Here, an investigation of the anti-cancer activity of GTN and the molecular signaling pathways of non-apoptotic cell death in the invasive human breast cancer MDA-MB-231 cell line were undertaken. Apoptotic cell death was suppressed by using a pan-caspase inhibitor (Benzyloxycarbonyl-Val-Ala-Asp-[O-methyl]-fluoromethylketone), z-VAD-fmk) as a model to study whether GTN induced caspase-independent cell death. In the anoikis study, MDA-MB-231 cells were cultured on poly-(2-hydroxyethyl methacrylate)-or poly-HEMA-coated plates to mimic anoikis-resistance growth and determine whether GTN induced cell death and the mechanisms involved. GTN and z-VAD-fmk induced human breast cancer MDA-MB-231 cells to undergo necroptosis via endoplasmic reticulum (ER) and oxidative stresses, with increased expressions of necroptotic genes such as rip1, rip3, and mlkl. GTN induced MDA-MB-231 cells to undergo anoikis via reversed epithelial-mesenchymal transition (EMT) protein expressions, inhibited the EGFR/FAK/Src survival signaling pathway, and decreased matrix metalloproteinase secretion.