PEG‐liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase‐8

Abstract

Since cellular uptake of PEG [poly(ethylene glycol)]-liposomal L-OHP (oxaliplatin) induces bioactive changes in CRC (colorectal cancer), we have investigated its apoptotic effect and anticancer mechanism. Human CRC SW480 cells were treated with PEG-liposomal L-OHP and a caspase-8 inhibitor [Z-IETD-FMK (benzyloxycarbonyl-Ile-Glu-Thr-dl-Asp-fluoromethylketone)]. Apoptosis was measured by FCM (flow cytometry) and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. Expression of Fas/FasL and cytochrome c was detected using FCM and an immunofluorescence assay. Expression of caspase-8, Bid, caspase-9, caspase-7 and activated caspase-3 (P17) was examined by Western blot analyses. The results indicated that PEG-liposomal L-OHP (28 μg/ml L-OHP) induced marked apoptosis in SW480 cells compared with 28 μg/ml free L-OHP. The expression levels of Fas, FasL, cytochrome c, caspase-9, caspase-7 and activated caspase-3 proteins were up-regulated, with a corresponding increase in apoptosis; however, expression of caspase-8 and Bid were down-regulated as apoptosis increased. When cells were treated with Z-IETD-FMK, apoptosis was inhibited, but there was little impact on the expression of Fas, FasL, cytochrome c, Bid, caspase-9, caspase-7 and activated caspase-3. These findings indicate that PEG-liposomal L-OHP enhances the anticancer potency of the chemotherapeutic agent; moreover, Fas/FasL and caspase-8 signalling pathways play a key role in mediating PEG-liposomal L-OHP-induced apoptosis.

Mechanism of ziram-induced apoptosis in human T lymphocytes

“…Moreover, because the Fas/Fas ligand pathway is an important trigger for apoptosis and upstream of caspase 8 activation (Yang et al 2011), the effect of ziram on Fas/ FasL should also be considered. Therefore, a study to investigate the influence of ziram on the Fas/FasL pathway is necessary in the future.…”

The fermented non-digestible fraction of common bean (Phaseolus vulgaris L.) triggers cell cycle arrest and apoptosis in human colon adenocarcinoma cells

“…2 Interaction among differentially modulated genes in the apoptosis biochemical pathway, using KEGG, after hgf-FNDF-LC 50 and SCFA-LC 50 treatments binding to its receptor Fas on the surface of CRC cells (Yang et al 2011). Some compounds, such as sodium butyrate, sensitize cancer cells (including HT-29) to p53-independent, Fas-mediated apoptosis (Bonnotte et al 1998;Yang et al 2012), suggesting this pathway as a mechanism for the treatments on the induction of extrinsic apoptosis by the treatments evaluated in this study. However, apoptosis may also be carried out through the mitochondrial pathway by several molecules such as the pro-apoptotic BID (upregulated 32-and 19.12-fold by both treatments, respectively; Table 1).…”

Application of liposomes in drug development – focus on gastroenterological targets

“…64 A large amount of effort has been dedicated to explore the formulation and characterization of PEG liposomal oxaliplatin (L-OHP). In the SW480 human CRC cell line, PEGylated 65 and by changing the expression of cyclins and influencing cell cycle arrest. 66 PEG liposomal L-OHP was found to preferably accumulate in tumor tissue after intravenous injection into CRC xenografted nude mice, which promoted antiapoptotic pathways while inhibiting proapoptotic pathways, and resulted in longer survival time.…”