Abstract
Goniothalamin is an active compound extracted from Goniothalamus griffithii, a local plant found in northern Thailand. Goniothalamin inhibits cancer cell growth but is also toxic to normal cells. The aims of this study were to identify the cytotoxic effect of goniothalamin and the mechanism of cell death in human HL-60 and U937 cells. Cytotoxicity was determined by MTT assay and cell cycle profiles were demonstrated by staining with propidium iodide (PI) and flow cytometry. Apoptosis was confirmed by staining with annexin V-FITC/propidium iodide (PI) and flow cytometry. Reduction of mitochondrial transmembrane potential was determined by staining with dihexyloxacarbocyanine iodide and flow cytometry and expression of Smac, caspase-8 and -9 was demonstrated by Western blotting. Goniothalamin inhibited growth of HL-60 and U937 cell lines. An increase of SubG1 phase was found in their cell cycle profiles, indicating apoptosis as the mode of cell death. Apoptosis was confirmed by the flip-flop of phosphatidylserine using annexin V-FITC/PI assay in HL60 and U937 cells in a dose response manner. Furthermore, reduction of mitochondrial transmembrane potential was found in both cell types while expression of caspase-8, -9 and Smac/Diablo was increased in HL-60 cells. Taken together, our results indicate that goniothalamin-treated human leukemic cells undergo apoptosis via intrinsic and extrinsic pathways.
Highlights
Among constituents from the stems of Goniothalamus griffithii is goniothalamin (GTN), a plant bioactive styryllactone (Mu et al, 2003)
Apoptosis was confirmed by the flip-flop of phosphatidylserine using annexin V-FITC/propidium iodide (PI) assay in HL60 and U937 cells in a dose response manner
Goniothalamin is cytotoxic towards both cancerous (HGC-27, MCF-7, PANC-1, HeLa) and non-cancerous (3T3) cells but these cells die via necrotic cell death (Ali et al, 1997)
Summary
Among constituents from the stems of Goniothalamus griffithii is goniothalamin (GTN), a plant bioactive styryllactone (Mu et al, 2003). GTN can be extracted from several other species of Goniothalamus such as Goniothalamus macrophyllus (Alabsi et al, 2012), Goniothalamus tapisoides Mat Salleh (Kim et al, 2012) and Goniothalamus andersonii (Inayat-Hussain et al, 1999). GTN induces apoptosis and autophagy in renal cancer cells and inhibits the nitric oxide synthase (NOS) activity and expression (de Fátima et al, 2008). GTN, a plant styrylpyrone derivative, induces apoptosis in Jurkat T-cells as assessed by the externalization of phosphatidylserine via caspase-3 and -7 activation (Inayat-Hussain et al, 1999). It induces leukemic HL-60 cell apoptosis via the loss of mitochondrial transmembrane potential and caspase-9 activation (Inayat-Hussain et al, 2003). Even though there are several reports of the apoptotic induction of GTN in many cancer cell lines, the involvement of extrinsic pathway remains elusive
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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.
