Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL‐induced apoptosis

Vaculová, Alena Hyršlová; Hofmanová, Jiřina; Souček, Karel; Anděra, Ladislav; Kozubı́k, Alois

doi:10.1016/j.febslet.2004.10.013

Cited by 15 publications

(18 citation statements)

References 28 publications

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“…Human colon adenocarcinoma HT-29 and SW620 cells (ATCC, Rockville, MD, USA) were cultured as described previously [7]. Twenty-four hours after seeding in McCoy's medium with 5% fetal calf serum, the cells were pre-treated with the MEK1/2 inhibitor-U0126 (10 lM), the PI3K inhibitor-LY294002 (50 lM) (Cell Signaling Technology), or vehicle (DMSO) alone for 45 or 60 min, respectively, and then treated with TRAIL (human recombinant Killer TRAIL, 100 ng/ ml, kindly provided by L. Anděra, IMG Prague, Czech Republic) for 4 h.…”

Section: Culture Conditionsmentioning

confidence: 99%

“…Interestingly, during colorectal carcinogenesis, a marked increase in sensitivity to the apoptotic effects of TRAIL, associated with progression from benign to malignant tumour type has been reported [6]. For this study, we have used the human colon adenocarcinoma cell line HT-29, which we previously characterized as type II cells [7], and SW620 cells, which are resistant to TRAIL-induced apoptosis, as models for colon cancer.…”

Section: Introductionmentioning

confidence: 99%

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Different modulation of TRAIL‐induced apoptosis by inhibition of pro‐survival pathways in TRAIL‐sensitive and TRAIL‐resistant colon cancer cells

Vaculová¹,

Hofmanová²,

Souček³

et al. 2006

FEBS Letters

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Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro-survival and apoptotic signals. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (HT-29) and TRAIL-resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL-induced apoptosis in HT-29 cells, but not in SW620 cells. We report a different regulation of the level of an anti-apoptotic Mcl-1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3b.

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Section: Culture Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Different modulation of TRAIL‐induced apoptosis by inhibition of pro‐survival pathways in TRAIL‐sensitive and TRAIL‐resistant colon cancer cells

Vaculová¹,

Hofmanová²,

Souček³

et al. 2006

FEBS Letters

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“…[20][21][22][23][24][25][26][27][28][29] Also, ethanol stimulates the TRAIL-induced apoptosis in leukemic T-lymphocytes and colon cancer cells in vitro. 38,39 Despite these data, an interactive effect of ethanol and TRAIL in promoting PCa cell death has not been studied.…”

Section: Discussionmentioning

confidence: 99%

“…Subconfluent cell cultures were exposed to TRAIL (100 ng ml À 1 ) and ethanol (4%) alone or in combination for 48 h in medium containing 5% FBS. TRAIL and ethanol concentrations were based on work by Shankar et al 12 and Vaculová et al, 38 respectively. Cells were treated with 5 mM N-acetyl-L-cystein (NAC) (Sigma Aldrich, St Louis, MO, USA) 1 h before TRAIL and ethanol treatment when necessary.…”

Section: Methodsmentioning

confidence: 99%

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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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Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs

Hofmanová

Vaculová

Koubková

et al. 2009

Molecular Nutrition Food Res

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We verified the hypothesis suggesting modulation of the effects of sodium butyrate (NaBt) by omega-3 or omega-6 PUFAs. Comparing the response of human colon epithelial cell lines of fetal (FHC) and adenocarcinoma (HT-29, HCT-116) origin, we detected significant differences in proliferation, differentiation and apoptotic response to the treatment of NaBt, arachidonic or docosahexaenoic acids and their combination. While in FHC and HT-29 cells NaBt induced G0/G1 arrest, differentiation and low level of apoptosis, in HCT-116 cells G2/M arrest, no differentiation and high degree of apoptosis were detected. Moreover, in FHC cells significant potentiation of apoptosis accompanied by increased arrest in the cell cycle, cell detachment and decrease in differentiation were detected after combined treatment with NaBt and both PUFAs. Changes in cytokinetics induced by fatty acids were accompanied by membrane lipid unpacking, reactive oxygen species (ROS) production, and decrease in mitochondrial membrane potential (MMP). Detection of caspase-3 activation and dynamic modulation of Mcl-1 protein expression imply their possible role in both cell differentiation and apoptotic response. Our results support the concept of modulation of NaBt effects by PUFAs, especially of omega-3 type, in colonic cells in vitro with diverse impact in cell lines derived from normal or neoplastic epithelium.

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Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL‐induced apoptosis

Cited by 15 publications

References 28 publications

Different modulation of TRAIL‐induced apoptosis by inhibition of pro‐survival pathways in TRAIL‐sensitive and TRAIL‐resistant colon cancer cells

Different modulation of TRAIL‐induced apoptosis by inhibition of pro‐survival pathways in TRAIL‐sensitive and TRAIL‐resistant colon cancer cells

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

Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs

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