| 1. |
- Banerji, Shantanu, et al.
(författare)
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Important differences between topoisomerase-I and -II targeting agents
- 2006
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Ingår i: Cancer Biology & Therapy. - : Landes Bioscience. - 1538-4047 .- 1555-8576. ; 5:8, s. 965-966
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Commentary to: Activation of ATM and Histone H2AX Phosphorylation Induced by Mitoxantrone But Not by Topotecan is Prevented by the Antioxidant N-acetyl-L-Cysteine Xuan Huang, Akira Kurose, Toshiki Tanaka, Frank Traganos, Wei Dai and Zbigniew Darzynkiewicz
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| 3. |
- Gu, Xiaolian, 1976-, et al.
(författare)
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TRAF4 is potently induced by TAp63 isoforms and localised according to differentiation in SCCHN
- 2007
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Ingår i: Cancer Biology & Therapy. - 1538-4047 .- 1555-8576. ; 6:12, s. 1979-1983
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Tidskriftsartikel (refereegranskat)abstract
- p63, a member of the p53 family, is overexpressed in squamous cell carcinoma of the head and neck (SCCHN) and some other tumors of epithelial origin. As a transcription factor, p63 can bind to p53-type response elements and there is some overlap between p53 family transcriptional targets. Tumor necrosis factor receptor associated factor 4 (TRAF4) is a p53 regulated gene which is overexpressed in many human carcinomas. We investigated the involvement of p63 in regulation of TRAF4 and the expression of the TRAF4 protein in SCCHN. Disrupting endogenous p63 expression resulted in downregulation of TRAF4 mRNA and protein in an SCCHN cell line. Endogenous p63 bound to the TRAF4 promoter in vivo and reporter assays showed that p63, p73 and p53 can all transactivate TRAF4, with TAp63 isoforms being the most potent activators. The level of TRAF4 activation by TAp63 was two-fold higher than by p53, and TRAF4 was ten-fold more responsive to TAp63 than another p63-target, IGFBP3. Nuclear expression of TRAF4 was seen in normal oral epithelium and highly/moderately differentiated SCCHN, whereas cytoplasmic expression of TRAF4 was seen in poorly differentiated SCCHN. These results indicate that TRAF4 is a common target of p53 family members and that localization of TRAF4 is associated with differentiation of SCCHN cells.
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| 4. |
- Itani, Wafica, et al.
(författare)
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Anti colon cancer components from lebanese sage (Salvia libanotica) essential oil : Mechanistic basis
- 2008
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Ingår i: Cancer Biology & Therapy. - : Informa UK Limited. - 1538-4047 .- 1555-8576. ; 7:11, s. 1765-1773
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Tidskriftsartikel (refereegranskat)abstract
- Lebanese sage essential oil possesses antitumor properties, however, the bioactive components and antitumor mechanisms are not known. Here we show that combining the three sage bioactive compounds, Linalyl acetate (Ly), Terpeniol (Te) and Camphor (Ca), caused synergistic inhibition of the growth of two isogenic human colon cancer cell lines HCT-116 (p53(+/+) and p53(-/-)), and had no effect on growth of FHs74Int normal human intestinal cell line. In p53(+/+) cells, the combination of Ly + Te + Ca (10(-3) M of each) caused significant accumulation of cells in PreG(1) (64% at 48 h); less preG(1) increase was observed in response to Ly + Te (25%) or Ly + Ca (14%). In p53(-/-) cells, Ly + Te + Ca caused cell accumulation in PreG(1) and G(2)/M phases. In response to the three components, 58% apoptosis occurred in p53(+/+) cells and 38% in p53(-/-) cells. Apoptosis by Ly + Te + Ca, in p53(+/+) cells, was associated with increased Bax/Bcl-2 ratio and pp53/p53 ratio, cleavage and activation of caspase-3, loss of mitochondrial membrane potential and cytochrome c release. In p53(-/-) cells, the disruption of mitochondrial membrane potential was observed but to a lesser extent than in p53(+/+) cells and caspase activation or cleavage did not appear to be involved in drug-induced apoptosis. Sage components induced poly(ADP-ribose)-polymerase (PARP) cleavage in both p53(+/+) and p53(-/-) cell lines. Pretreatment with the caspase-3 inhibitor and pan caspase inhibitor abrogated drug-mediated apoptosis and blocked procaspase-3 activation and partially blocked PARP cleavage in p53(+/+) cells. Conversely, in p53(-/-) cells, pre-incubation with caspase inhibitors potentiated drug-induced cell death. It appears that apoptosis in p53(+/+) cells is through the mitochondrial-mediated, caspase-dependent pathway, while in p53(-/-) cells apoptosis is mostly caspase independent despite the presence and features indicating caspase-dependent cell death, such as cytochrome c release and PARP cleavage. Our findings encourage further studies of sage oil components as promising chemotherapeutic agents against colon cancer.
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| 5. |
- Johansson, David, et al.
(författare)
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Verotoxin-1 Induction of Apoptosis in Gb3-Expressing Human Glioma Cell Lines
- 2006
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Ingår i: Cancer Biology & Therapy. - 1538-4047 .- 1555-8576. ; 5:9, s. 1211-1217
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the cytotoxicity and mechanism of apoptosis induction of verotoxin-1 (VT-1) in human glioma cell lines. VT-1 is a member of the shiga-toxin family expressed by some serotypes of Escherichia coli and Shigella dysenteriae. Shiga-toxins have been shown to induce apoptosis by binding to its membrane receptor Gb3. The human glioma cell lines SF-767, U-343 MG, and U-251 MG were studied together with BT4C, a rat glioma cell line. Cells were first screened for Gb3 expression by flow cytometry. Fluorescein diacetate was used to determine cell viability after VT-1 and irradiation exposure and apoptosis was studied by TUNEL staining, a mitochondrial membrane potential assay, and caspase activity assays. SF-767 and U-343 MG cells were found to express Gb3 and were also sensitive to VT-1-induced cytotoxicity, whereas nonGb3-expressing U-251 MG and BT4C glioma cells were not. VT-1 depolarized the mitochondrial membrane and activated caspase-9 and -3 of SF-767 and U-343 MG cells. VT-1 exposure for 72 h resulted in approx. 60 and 90% TUNEL-stained cells, respectively. D, L-Threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) an inhibitor of glucosylceramide synthesis was used to block Gb3 synthesis. Two mumol/L PPMP for 72 h abolished SF-767 and U-343 MG expression of Gb3 and made the cells completely resistant to VT-1 induced apoptosis. Key components of MAP kinase signalling pathways that control BAX and mitochondrial function were investigated. VT-1 induced JNK phosphorylation in both cell lines, suggesting that survival signal pathways were overruled by VT-1-induced JNK activation leading to mitochondrial depolarization, caspase-9 activation and apoptosis. Immunohistochemistry of cryostat section from glioma biopsies demonstrated expression of Gb3 was in the vascular endothelial cells as well as tumor cells, but not in astrocytes. The high specificity and apoptosis inducing properties of verotoxin-1 indicates that the toxin may be a potential anti-neoplastic agent for Gb3-expressing gliomas.
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| 7. |
- Maddika, Subbareddy, et al.
(författare)
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Cancer-selective therapy of the future : Apoptin and its mechanism of action
- 2006
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Ingår i: Cancer Biology & Therapy. - : Landes Bioscience. - 1538-4047 .- 1555-8576. ; 5:1, s. 10-19
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Forskningsöversikt (refereegranskat)abstract
- Classical chemotherapy that specifically targets rapidly proliferating cells has been in existence for over eighty years and has proven to be fully successful in only a limited number of cancers. Thus, this review focuses on a novel, emerging approach for cancer therapy that uses alternative, and more unique features of cancer cells. This new approach facilitates the selective targeting of cancer, while sparing normal, non-transformed cells. Examples of molecules that kill cancer cells selectively are: apoptin, E4orf4, viral protein R (VpR), and Brevinin-2R. Below we focus on apoptin, a product of the third open reading frame (VP3) of the chicken anemia virus. Besides discussing apoptin's mechanism of action, we also provide concise insight into the biology of a chicken anemia virus infection. Since apoptin's cancer-selective toxicity depends on its nuclear localization, we broadly discuss mechanism(s) involved in its nuclear retention (both nuclear import and export). We also discuss recent findings on apoptin's molecular mechanism of action, with a focus on the role of Nur77 in apoptin's nucleo-cytoplasmic signaling. Finally, we compare the current findings on apoptin to the mechanism of cancer selective toxicity of E4orf4. In the 'summary' section, besides highlighting important issues related to cancer-selective therapy, we also discuss concurrent approaches towards therapy personalization, particularly those related to the in vivo, and real time cancer therapy efficacy monitoring, using "lab-on-the-chip" and other emerging technologies.
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