Inhibition of Akt signaling by the lignan matairesinol sensitizes prostate cancer cells to TRAIL-induced apoptosis

Peuhu, Emilia; Rivero-Müller, Adolfo; Stykki, H; Torvaldson, Elin; Holmbom, Thomas; Eklund, Patrik; Unkila, Mikko; Sjöholm, Rainer; Eriksson, John E.

doi:10.1038/onc.2009.386

Cited by 44 publications

(31 citation statements)

References 40 publications

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“…Pro-survival factors, particularly Akt is a constitutively active in PCa cells, promoting their survival and resistance to chemotherapy. [40][41][42][43][44]47,48 Thus, targeting Akt activity with a combination of agents is a promising approach to promote responsiveness to TRAIL as supported by our current results. Additionally, ethanol enhanced TRAIL's effects including caspase activation and PARP cleavage in LNCaP cells, which are inherently resistant to TRAIL.…”

Section: Discussionsupporting

confidence: 66%

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

Plante

Arscott

Folsom

et al. 2012

Prostate Cancer Prostatic Dis

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BACKGROUND: Effective treatment of prostate cancer (PCa) remains a major challenge due to chemoresistance to drugs including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Ethanol and ethanol extracts are known apoptosis inducers. However, cytotoxic effects of ethanol on PCa cells are unclear. METHODS: In this study we utilized PC3 and LNCaP cell culture models. We used immunohistochemical analysis, western blot analysis, reactive oxygen species (ROS) measurement, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) Cell Proliferation Assay, Annexin-V staining and flow cytometry for quantification of apoptosis. In vitro soft agar colony formation and Boyden chamber invasion assays were used. Tumorigenicity was measured in a xenotransplantation mouse model. RESULTS: Here, we demonstrate that ethanol enhances the apoptosis-inducing potential of TRAIL in androgen-resistant PC3 cells and sensitizes TRAIL-resistant, androgen sensitive LNCaP cells to apoptosis through caspase activation, and a complete cleavage of poly (ADP)-ribose polymerase, which was in association with increased production of ROS. The cytotoxicity of ethanol was suppressed by an antioxidant N-acetyl cystein pretreatment. Furthermore, ethanol in combination with TRAIL increased the expression of cyclin-dependent kinase inhibitor p21 and decreased the levels of Bcl-2 and phosphorylated-AKT. These molecular changes were accompanied by decreased proliferation, anchorage-independent growth and invasive potential of PC3 and LNCaP cells. In vivo studies using a xenotransplantation mouse model with PC3 cells demonstrated significantly increased apoptosis in tumors treated with ethanol and TRAIL in combination. CONCLUSIONS: Taken together, use of ethanol in combination with TRAIL may be an effective strategy to augment sensitivity to TRAIL-induced apoptosis in PCa cells.

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Section: Discussionsupporting

confidence: 66%

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

Plante

Arscott

Folsom

et al. 2012

Prostate Cancer Prostatic Dis

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“…After treatment with XN (0, 1, 5, 10, or 20 mM) for 48 h, the cells were collected and fixed in ice-cold 80% ethanol at À20 C for 24 h. Next, the cells were washed in phosphate-buffered saline (PBS), resuspended in 0.5 ml of staining buffer (BD Biosciences) containing propidium iodide (PI)/RNase, and incubated in the dark for 30 min at room temperature. The cells were further analyzed with a FACSCalibur flow cytometer (BD Dickinson, San Jose, CA, USA) equipped with a 488-nm argon-ion laser as previously described (Peuhu et al, 2010;Tran et al, 2003). The distribution of cells in distinct cell cycle phases was evaluated using noncommercial flow cytometry analyzing softwareCylchred Version 1.0.2 for Windows (source: University of Wales, Cardiff, Wales, UK) and WinMDI 2.9 for Windows (source: facs.…”

Section: Analysis Of Cell Cycle By Flow Cytometrymentioning

confidence: 99%

Xanthohumol inhibits the extracellular signal regulated kinase (ERK) signalling pathway and suppresses cell growth of lung adenocarcinoma cells

et al. 2016

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“…Arctiin, matairesinol, and arctigenin reduced the growth of human colon cancer SW480 cells through the inhibition of the Wnt/b-catenin signaling pathway (12). Matairesinol sensitized the androgen-dependent prostate cancer LNCaP cells to TRAILinduced apoptosis by reducing the Akt activity (13), in addition, 7-hydroxymatairesinol inhibited the growth of LNCaP tumor xenografts in athymic mice in vivo, increasing the apopotosis index and reducing the proliferation index of the tumor mass (14). Sesamin induced growth arrest at the G1 phase of the cell cycle in the human breast cancer MCF-7 cells by suppressing the cyclin D1 protein expression (15).…”

Section: Introductionmentioning

confidence: 99%

Pinoresinol Inhibits Proliferation and Induces Differentiation on Human HL60 Leukemia Cells

Sepporta

Mazza

Morozzi

et al. 2013

Nutrition and Cancer

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Pinoresinol (PIN), one of the simplest lignans, is the precursor of other dietary lignans that are present in whole-grain cereals, legumes, fruits, and other vegetables. Several experimental and epidemiological evidences suggest that lignans may prevent human cancer in different organs. In this study we investigated the chemopreventive properties of PIN on cell lines derived from different sites either expressing or not the functional tumor suppressor protein p53. It was found that PIN inhibited the proliferation of p53 wild type colon and prostate tumor cells (HCT116 and LNCaP) while in breast cells the inhibition of growth was observed only in p53 mutant cells (MDA-MB-231). A potent antiproliferative activity of PIN was also observed on p53 null cells HL60 (IC50% 8 μM), their multidrug resistant variant HL60R (IC50% 32 μM) and K562. On HL60 cells, PIN caused a block of cell cycle in the G0/G1 phase, induced a weak proapoptotic effect but it was a good trigger of differentiation (NBT reduction and CD11b expression). PIN caused an upregulation of the CDK inhibitor p21(WAF1/Cip1) both at mRNA and protein levels so suggesting that this could be a mechanism by which PIN reduced proliferation and induced differentiation on HL60 cells.

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Inhibition of Akt signaling by the lignan matairesinol sensitizes prostate cancer cells to TRAIL-induced apoptosis

Cited by 44 publications

References 40 publications

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

Xanthohumol inhibits the extracellular signal regulated kinase (ERK) signalling pathway and suppresses cell growth of lung adenocarcinoma cells

Pinoresinol Inhibits Proliferation and Induces Differentiation on Human HL60 Leukemia Cells

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