Abstract
Goniothalamin (GTN), a styryl-lactone, exhibits inhibitory effects on many kinds of cancer cells in vitro. The objectives of this study were to investigate the anticancer activities of GTN and molecular signaling pathways associated with cell death in human breast cancer MDA-MB-231 cell line. GTN inhibited the growth of MDA-MB-231 cells. Apoptosis was confirmed by annexin V-FITC and PI staining, and apoptotic morphology was observed by microscopy. Reduction of mitochondrial transmembrane potential and enhanced caspases activities were found in GTN-treated MDA-MB-231 cells. GTN significantly altered apoptosis-related protein expressions, including Noxa, PUMA, Bax, Bim, Bad, Bcl-2, Bcl-xL, and DIABLO, which was related to the gene expression levels. Mitochondrial calcium released to the cytosol and ER stress related proteins increased, which correlated with increases in ER stress gene expression levels. GTN induced hydrogen peroxide and superoxide anion radicals in MDA-MB-231 cells associated with cell cycle arrest in G2/M phase, which was induced by phosphorylation and ATM gene expression. Moreover, GTN had synergistic effects when combined with cyclophosphamide, 5-fluorouracil, paclitaxel, and vinblastine, and additive effect with methotrexate through caspases enzyme-acceleration. In conclusion, goniothalamin-induced MDA-MB-231 cell apoptosis occurred via intrinsic and extrinsic pathways, along with ER stress. These pathways provide new targeted drug strategies for advancements in anticancer medicine.
Highlights
Goniothalamin (GTN) is isolated and characterized from Goniothalamus griffithii [1]
To determine the cytotoxic effect and cell cycle distribution histogram of goniothalamin-treated MDA-MB-231 cells, GTN was found to be toxic against MDA-MB-231 cells at 24 hours of treatment (Figure 1(a)) with an inhibitory concentration of 50 percent (IC50) at 37 μM
Cell cycle progression is an event responding to DNA damage, which is usually signaled via the ataxia telangiectasia mutated (ATM)/ATR/p53/p21 pathway [28]
Summary
Goniothalamin (GTN) is isolated and characterized from Goniothalamus griffithii [1]. It has been widely used as a folk medicine in south-east Asia. GTN induces apoptosis in Jurkat T-cells via caspase-3,-7 and PARP-cleavage [3] and intrinsic apoptosis in human promyelocytic leukemia HL-60 cells [4]. The apoptosis induction pathway depends on the cancer cell type [1]. GTN induces cell cycle arrest at the G2/M phase in human breast cancer MDA-MB-231 cells [5]. GTN causes DNA damage, which subsequently leads to apoptosis in many cell lines [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
