Goniothalamin Induces Necroptosis and Anoikis in Human Invasive Breast Cancer MDA-MB-231 Cells

• Published in: International journal of molecular sciences Vol. 20; no. 16; p. 3953
• Main Authors: Khaw-On, Patompong, Pompimon, Wilart, Banjerdpongchai, Ratana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.08.2019; MDPI
• Subjects: Alkylation; Anoikis; Anoikis - drug effects; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis-inducing factor; BAX protein; Bcl-2 protein; Bcl-x protein; Biomarkers; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - ultrastructure; Calcium - metabolism; Caspase; Caspase inhibitors; Caspases - metabolism; Cell adhesion; Cell adhesion & migration; Cell cycle; Cell death; Cell Line, Tumor; Cytosol - metabolism; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; Epidermal growth factor receptors; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; ErbB Receptors - metabolism; Extracellular matrix; Female; Focal Adhesion Kinase 1 - metabolism; goniothalamin; Growth factors; Humans; Invasiveness; Kinases; Ligands; Membrane permeability; Metastasis; Mitochondria; Necroptosis; Necroptosis - drug effects; Necrosis; Oxidative stress; pan-caspase inhibitor; Permeability; Poly(ADP-ribose) polymerase; Proteins; Pyrones - pharmacology; Reactive Oxygen Species - metabolism; Regulators; Signal Transduction - drug effects; Src protein; src-Family Kinases - metabolism; Tumor necrosis factor-TNF; goniothalamin; anoikis; breast cancer; pan-caspase inhibitor; epithelial-mesenchymal transition; necroptosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20163953

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 , , and . 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.