α-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells

Abstract

Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of α-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage.

Vitamin E synthetic derivate—TPGS—selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia

“…The ability of cells to form formazan crystals by active mitochondrial respiration was determined using a Stat Fax 3200 microplate spectrophotometer (Awareness Technology, Palm City, Florida, USA) after dissolving the crystals in DMSO, according to Ref. [23]. The absorbance, measured at 570 nM, was proportional to the number of viable cells per well.…”

Superior antitumor effect of self-assembly supramolecular paclitaxel nanoparticles

“…Enzymatic activity of Caspase-3 could be rapidly initiated by the caspase cascade reaction. [35][36][37] In this study, cleaved fragments of Caspase-3 (Cle-C3) were much higher in Ptx-NPs treated group than the free Ptx treated group, again conrming enhanced induction of apoptosis by Ptx-NPs. Double staining and FACS were performed to observe apoptosis aer treatments.…”

α- Tocopherol succinate loaded nano-structed lipid carriers improves antitumor activity of doxorubicin in breast cancer models in vivo

“…The molecular mechanism remains unclear, however TX treatment leads to proliferation inhibition and induction of apoptosis in cancer cells [9]. There are some studies reporting that the combination with TS increased the antitumor activity of chemotherapeutics, including paclitaxel [10] and doxorubicin [11]. …”