The sequential treatment with ionizing radiation followed by TRAIL/Apo-2L reduces tumor growth and induces apoptosis of breast tumor xenografts in nude mice

MS-275 Sensitizes TRAIL-Resistant Breast Cancer Cells, Inhibits Angiogenesis and Metastasis, and Reverses Epithelial-Mesenchymal Transition In vivo

“…Sequential treatments of nude mice with MS-275 followed by TRAIL caused a synergistic apoptotic response through the activation of caspase-3, which was accompanied by regression of tumor growth and inhibition of markers of angiogenesis and metastasis. Together with previous studies showing that cancer chemotherapeutic drugs, irradiation, and HDAC inhibitor SAHA upregulate DR4 and/or DR5 expression (6,10,11,34), our data also show that MS-275 can upregulate these death receptors in TRAIL-resistant breast cancer xenografts. Although we have recently shown the additive or synergistic effects of HDAC inhibitors and TRAIL on apoptosis in several cancers (5,6,26), this is the first study showing that the MS-275 can reverse EMT in breast tumor tissues and thus may be responsible for reduced metastasis.…”

“…Although many cancer cells undergo TRAIL-induced apoptosis, some cells are resistant to TRAIL, making it ineffective as an anticancer agent (10)(11)(12). Expression of certain apoptosisrelated genes has been suggested to regulate sensitivity of cancer cells to TRAIL-mediated apoptosis, including NF-kB (13), Akt/PKB (14), Bcl-2 (15), Bax and/or Bak (16), and c-FLIP (17).…”

Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer

“…We have previously shown that the activation of caspase-3 by stress stimuli leads to cleavage of several substrates including Poly-ADP Ribose Polymerase (PARP) (47,(50)(51)(52). We therefore examined the activation of caspase-3 and cleavage of PARP by immunofluorescence technique (Fig.…”

Combined treatment of colorectal tumours with agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and radiotherapy: enhanced effects in vitro and dose-dependent growth delay in vivo

“…Death receptor stimulation alone often results only in a temporary tumour cell reduction. However, combined modality treatment of irradiation and TRAIL receptor stimulation enhances the rate of cell death when compared to either treatment alone (Chinnaiyan et al, 2000;Belka et al, 2001;Kim et al, 2001;Shankar et al, 2004a;Marini et al, 2005). Initial results of phase 1 clinical studies for both antibodies show good compatibility and only mild non-specific toxicity in a wide array of haematopoietic and solid malignancies (de Bono et al, 2004;Hotte et al, 2004).…”