benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Colorectal-Neoplasms

benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone has been researched along with Colorectal-Neoplasms* in 11 studies

Other Studies

11 other study(ies) available for benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Colorectal-Neoplasms

ArticleYear
Heterocyclic organobismuth(III) compound induces nonapoptotic cell death via lipid peroxidation.
    Anti-cancer drugs, 2020, Volume: 31, Issue:1

    Heterocyclic organobismuth compounds, such as N-tert-butyl-bi-chlorodibenzo[c,f][1,5]azabismocine (compound 1) and bi-chlorodibenzo[c,f ][1,5]thiabismocine (compound 3), exert potent antiproliferative activities in vitro in human cancer cell lines. We showed that compound 3 induced both apoptotic and nonapoptotic cell death via reactive oxygen species production and mitotic arrest in a dose-dependent manner. The mechanisms underlying the dose-dependent effect of these organobismuth compounds were not clear. In the present study, we examined the dose-dependent mechanism underlying cell death induced by compound 1 in a human pancreatic cancer cell line, SUIT-2, and a human colorectal cancer cell line, DLD-1. Compound 1 inhibited cell growth in a dose-dependent manner and induced cell death. Treatment with the pan-caspase inhibitor zVAD-fmk reduced cell death induced by compound 1, whereas the inhibitory effect of zVAD-fmk was limited. Moreover, compound 1 significantly induced lipid peroxidation with concomitant induction of caspase-independent cell death. Our results suggested that eight-membered ring organobismuth compounds induce nonapoptotic cell death via lipid peroxidation.

    Topics: alpha-Tocopherol; Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Bismuth; Caspase Inhibitors; Cell Death; Cell Line, Tumor; Cell Membrane; Colorectal Neoplasms; Dose-Response Relationship, Drug; HeLa Cells; Humans; Isoquinolines; Lipid Peroxidation; Organometallic Compounds; Pancreatic Neoplasms; Reactive Oxygen Species

2020
Malformin A1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through stimulation of the p38 signaling pathway.
    International journal of oncology, 2017, Volume: 51, Issue:3

    Malformin A1 (MA1), a cyclic pentapeptide isolated from Aspergillus niger, has been found to possess a range of bioactive properties including antibacterial activity. However, it is unclear whether MA1 exerts an anticancer effect or not. In this study, we conducted in vitro experiments to investigate its anticancer properties in human colorectal cancer cells. The effect of MA1 on human colorectal cancer cells, SW480 and DKO1, was examined by the WST-1 cell viability assay, inverted microscopy, 5-bromo-2-deoxyuridine (BrdU) incorporation, flow cytometry, DNA fragmentation, wound healing, Transwell assays, and western blotting. MA1 treatment showed potent cytotoxic activities on human colorectal cancer cells. MA1 treatment induced apoptosis by activating the poly(ADP-ribose) polymerase (PARP), caspase‑3, -7, and -9. MA1 treatment led to the increase in p53 upregulated modulator of apoptosis (PUMA) and the decrease in X-linked inhibitor of apoptosis protein (XIAP) and Survivin. In addition, MA1 treatment induced cell cycle arrest in the sub-G1 phase. The pan-caspase inhibitor, Z‑VAD‑FMK, attenuated these MA1-induced apoptotic effects on human colorectal cancer cells. Moreover, MA1 treatment suppressed tumor cell migration and invasion. The phosphorylation level of p38 was upregulated by MA1 treatment, and the inhibitor of p38, SB203580, attenuated the MA1-induced p38 phosphorylation as well as caspase‑3 and PARP activation. These results indicate that MA1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through the stimulation of the p38 signaling pathway.

    Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Apoptosis Regulatory Proteins; Caspase 3; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Survival; Colorectal Neoplasms; DNA Fragmentation; Humans; Imidazoles; MAP Kinase Signaling System; Neoplasm Invasiveness; p38 Mitogen-Activated Protein Kinases; Peptides, Cyclic; Phosphorylation; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins; Pyridines; Tumor Suppressor Protein p53; X-Linked Inhibitor of Apoptosis Protein

2017
A peptide-based positron emission tomography probe for in vivo detection of caspase activity in apoptotic cells.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2014, Apr-15, Volume: 20, Issue:8

    Apoptosis, or programmed cell death, can be leveraged as a surrogate measure of response to therapeutic interventions in medicine. Cysteine aspartic acid-specific proteases, or caspases, are essential determinants of apoptosis signaling cascades and represent promising targets for molecular imaging. Here, we report development and in vivo validation of [(18)F]4-fluorobenzylcarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone ([(18)F]FB-VAD-FMK), a novel peptide-based molecular probe suitable for quantification of caspase activity in vivo using positron emission tomography (PET).. Supported by molecular modeling studies and subsequent in vitro assays suggesting probe feasibility, the labeled pan-caspase inhibitory peptide, [(18)F]FB-VAD-FMK, was produced in high radiochemical yield and purity using a simple two-step, radiofluorination. The biodistribution of [(18)F]FB-VAD-FMK in normal tissue and its efficacy to predict response to molecularly targeted therapy in tumors was evaluated using microPET imaging of mouse models of human colorectal cancer.. Accumulation of [(18)F]FB-VAD-FMK was found to agree with elevated caspase-3 activity in response to Aurora B kinase inhibition as well as a multidrug regimen that combined an inhibitor of mutant BRAF and a dual PI3K/mTOR inhibitor in (V600E)BRAF colon cancer. In the latter setting, [(18)F]FB-VAD-FMK PET was also elevated in the tumors of cohorts that exhibited reduction in size.. These studies illuminate [(18)F]FB-VAD-FMK as a promising PET imaging probe to detect apoptosis in tumors and as a novel, potentially translatable biomarker for predicting response to personalized medicine.

    Topics: Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Caspase 3; Caspase Inhibitors; Cell Line, Tumor; Colonic Neoplasms; Colorectal Neoplasms; Female; Fluorine Radioisotopes; Fluorobenzenes; Humans; Imidazoles; Immunoblotting; Immunohistochemistry; Indoles; Mice, Inbred C57BL; Mice, Nude; Organophosphates; Peptides; Positron-Emission Tomography; Protein Kinase Inhibitors; Quinazolines; Quinolines; Radiopharmaceuticals; Sulfonamides; Tissue Distribution; Xenograft Model Antitumor Assays

2014
A novel small-molecule YLT205 induces apoptosis in human colorectal cells via mitochondrial apoptosis pathway in vitro and inhibits tumor growth in vivo.
    Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2014, Volume: 33, Issue:4

    Colorectal cancer continues to be one of the most common causes of cancer death, and the poor survival rates and liver metastases at the time of diagnosis urgently need more effective strategy for colorectal cancer treatment.. The activities of N-(5-bromopyridin-2-yl)-2-((6-(2-chloroacetamido)benzo[d]thiazol-2-yl)thio)acetamide (YLT205), which is a novel small molecule compound synthesized by us, were investigated using MTT assay, flow cytometry, western blotting and mice tumor xenograft models.. YLT205 induced apoptosis of human colorectal cell lines in a dose-dependent manner. The occurrence of apoptosis was associated with activation of caspases-9 and -3, down-regulation of Bcl-2 and up-regulation of Bax in HCT116 cells. Moreover, YLT205 disrupted mitochondrial membranes and induced the release of cytochrome c into cytosol. Impaired phosphorylation of p44/42 mitogen-activated protein kinase was also observed while the expression of phosphorylated protein kinase B (Akt) was not affected. Furthermore, in HCT116 and SW620 tumor-bearing nude mice models, YLT205 dose-dependently inhibited tumor growth without obvious adverse effects. Immunohistochemistry analyses revealed YLT205 also induced apoptosis and inhibited tumor cell proliferation in vivo.. These studies suggested that YLT205 might be a potential drug candidate for human colorectal cancer therapy.

    Topics: Acetamides; Amino Acid Chloromethyl Ketones; Animals; Apoptosis; bcl-2-Associated X Protein; Benzothiazoles; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Cytochromes c; Down-Regulation; Flavonoids; HCT116 Cells; Humans; Membrane Potential, Mitochondrial; Mice; Mice, Nude; Mitochondria; Phosphorylation; Transplantation, Heterologous

2014
A novel synthetic C-1 analogue of 7-deoxypancratistatin induces apoptosis in p53 positive and negative human colorectal cancer cells by targeting the mitochondria: enhancement of activity by tamoxifen.
    Investigational new drugs, 2012, Volume: 30, Issue:3

    The natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis plant, specifically induces apoptosis in many cancer cell lines. Unlike many other chemotherapeutics, PST is not genotoxic and has minimal adverse effects on non-cancerous cells. However, its availability for preclinical and clinical work is limited due to its low availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7-deoxypancratistatin with different modifications at C-1 were synthesized and screened for apoptosis inducing activity in human colorectal cancer (CRC) cells. We found that a C-1 acetoxymethyl derivative of 7-deoxypancratistatin, JC-TH-acetate-4 (JCTH-4), was effective in inducing apoptosis in both p53 positive (HCT 116) and p53 negative (HT-29) human CRC cell lines, demonstrating similar efficacy to that of natural PST. JCTH-4 was able to decrease mitochondrial membrane potential (MMP), increase levels of reactive oxygen species in isolated mitochondria, cause release of the apoptogenic factor cytochrome c (Cyto c) from isolated mitochondria, and induce autophagy in HCT 116 and HT-29 cells. Interestingly, when JCTH-4 was administered with tamoxifen (TAM), there was an enhanced effect in apoptosis induction, reactive oxygen species (ROS) production and Cyto c release by isolated mitochondria, and autophagic induction by CRC cells. Minimal toxicity was exhibited by a normal human fetal fibroblast (NFF) and a normal colon fibroblast (CCD-18Co) cell line. Hence, JCTH-4 is a novel compound capable of selectively inducing apoptosis and autophagy in CRC cells alone and in combination with TAM and may serve as a safer and more effective alternative to current cancer therapies.

    Topics: Amaryllidaceae Alkaloids; Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Apoptosis; Caspase Inhibitors; Caspases; Cell Line; Colorectal Neoplasms; Cysteine Proteinase Inhibitors; HCT116 Cells; HT29 Cells; Humans; Isoquinolines; Mitochondria; Reactive Oxygen Species; Selective Estrogen Receptor Modulators; Tamoxifen; Tumor Suppressor Protein p53

2012
COX-2-independent induction of apoptosis by celecoxib and polyamine naphthalimide conjugate mediated by polyamine depression in colorectal cancer cell lines.
    International journal of colorectal disease, 2012, Volume: 27, Issue:7

    Polyamine metabolism is an intriguing tumor therapeutic target. The present study was designed to assess the synergistic antitumor effects of NPC-16, a novel polyamine naphthalimide conjugate, with celecoxib and to elucidate the mechanism of these effects on human colorectal cancer cells.. Cell proliferation was assessed by the MTT assay. Cell apoptosis and mitochondria membrane potential were evaluated by high content screening analysis. Intracellular polyamine content was detected by HPLC. Protein expression was detected by western blot analysis.. The co-treatment with celecoxib enhanced NPC-16-induced apoptosis in HCT116 (COX-2 no expression), HT29 (COX-2 higher expression) and Caco-2 (COX-2 higher expression) colorectal cancer cells, which was mediated by the elevated NPC-16 uptake via the effect of celecoxib on polyamine metabolism, including the up-regulated spermidine/spermine N(1)-acetyltransferase (SSAT) activity and reduced intracellular polyamine levels. The presence of celecoxib does not result in obviously different effect on the NPC-16-triggered apoptosis in diverse COX-2 expressed colorectal cell lines, suggesting that COX-2 was not one vital factor in the apoptotic mechanism. Furthermore, this synergistic apoptosis was involved in the PKB/AKT signal pathway, Bcl-2 and caspase family members. Z-VAD-FMK, a cell permeable pan caspase inhibitor, almost completely inhibited celecoxib and NPC-16 co-induced apoptosis, indicating that this apoptosis was caspase dependent.. Co-treatment of celecoxib and NPC-16 could induce colorectal cancer cell apoptosis via COX-2-independent and caspase-dependent mechanisms. The combination therapy with these agents might provide a novel therapeutic model for colorectal cancer.

    Topics: Acetyltransferases; Amino Acid Chloromethyl Ketones; Apoptosis; Caspases; Celecoxib; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Cyclooxygenase 2; Cytochromes c; Drug Synergism; Enzyme Activation; Humans; Membrane Potential, Mitochondrial; Naphthalimides; Polyamines; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Pyrazoles; Sulfonamides; Up-Regulation

2012
Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53.
    Cancer letters, 2011, Feb-28, Volume: 301, Issue:2

    Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and significantly increased the levels of the pro-apoptotic regulator, Bax, while decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53 significantly blocked Rh2-induced cell death as well as vacuole formation, suggesting that both types of cell death induced by Rh2 are mediated by p53 activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF-κB survival pathway. Blockage of ROS by NAC or catalase inhibited the activation of NF-κB signaling and enhanced Rh2-induced cell death, suggesting that the anti-cancer effect of Rh2 can be enhanced by antioxidants.

    Topics: Acetylcysteine; Amino Acid Chloromethyl Ketones; Apoptosis; Apoptosis Regulatory Proteins; Blotting, Western; Caspase Inhibitors; Caspases; Cell Death; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Free Radical Scavengers; Ginsenosides; HCT116 Cells; HEK293 Cells; Humans; Mutation; NF-kappa B; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53; Vacuoles

2011
Irreversible pan-ErbB tyrosine kinase inhibitor CI-1033 induces caspase-independent apoptosis in colorectal cancer DiFi cell line.
    Apoptosis : an international journal on programmed cell death, 2005, Volume: 10, Issue:5

    The epidermal growth factor receptor (EGFR) is overexpressed in the majority of colorectal carcinomas and represents a target for therapeutic interventions with signal transduction inhibitors. We investigated the ability of CI-1033 to induce apoptosis and inhibition of proliferation in the colorectal cancer cell lines DiFi and Caco-2, which both express high levels of EGFR. While in Caco-2 cells CI-1033 treatment at a concentration 0.1 microM for 72 hours demonstrated only antiproliferative (53.7 +/- 4.3%) but no pro-apoptotic effects, treatment of DiFi cells resulted in a reduced proliferation rate (31.4 +/- 3.1%) and in apoptosis (44.2 +/- 8.9%). In order to define proteins involved in the regulation of apoptosis, we aimed to determine differences in the proteome profile of both cell lines before and after treatment with CI-1033. Cellular proteins were analyzed by 2-D gel electrophoresis followed by computational image analysis and mass spectrometry. Our data show that DiFi cells differ from Caco-2 cells in nine significantly upregulated proteins, and their potential role in apoptosis is described. We demonstrate that induction of apoptosis was triggered via caspase-independent pathways. Overexpression of leukocyte elastase inhibitor (LEI) and translocation of cathepsin D to the cytosol accompanied by upregulation of other defined proteins resulted in Bax-independent AIF translocation from mitochondria into the nucleus and apoptosis. Definition of these proteins can pave the way for functional studies and contribute to a better understanding of the effects of CI-1033 and the pathways of caspase-independent cell death.

    Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Apoptosis Inducing Factor; Caco-2 Cells; Caspase 3; Caspases; Cathepsin D; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Gefitinib; Genes, Tumor Suppressor; Humans; Morpholines; Proto-Oncogene Proteins c-bcl-2; Quinazolines; Receptor, ErbB-2; Serpins

2005
Overexpression of the human inducible nitric oxide synthase gene enhances radiation-induced apoptosis in colorectal cancer cells via a caspase-dependent mechanism.
    Nitric oxide : biology and chemistry, 2003, Volume: 8, Issue:2

    Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation.

    Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Caspase Inhibitors; Caspases; Cell Line, Tumor; Colorectal Neoplasms; Combined Modality Therapy; Cysteine Proteinase Inhibitors; Gene Expression Regulation, Neoplastic; Genetic Therapy; Humans; Lac Operon; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Radiation-Sensitizing Agents; S-Nitroso-N-Acetylpenicillamine; Time Factors; Transduction, Genetic

2003
Death of HT29 adenocarcinoma cells induced by TNF family receptor activation is caspase-independent and displays features of both apoptosis and necrosis.
    Cell death and differentiation, 2002, Volume: 9, Issue:12

    The HT29 adenocarcinoma is a common model of epithelial cell differentiation and colorectal cancer and its death is an oft-analyzed response to TNF family receptor signaling. The death event itself remains poorly characterized and here we have examined the involvement of caspases using pan-caspase inhibitors. zVAD-fmk did not block death of HT29 cells in response to activation of the Fas, TRAIL, TNF, TWEAK and LTbeta receptors. The secondary induction of TNF or the other known bona fide death inducing ligands did not account for death following LTbeta receptor activation indicating that TNF family receptors can trigger a caspase-independent death pathway regardless of the presence of canonical death domains in the receptor. To provide a frame of reference, the phenotype of HT29 death was compared to four other TNF family receptor triggered death events; Fas induced Jurkat cell apoptosis, TNF/zVAD induced L929 fibroblast necrosis, TNF induced death of WEHI 164 fibroblastoid cells and TNF/zVAD induced U937 death. The death of HT29 and U937 cells under these conditions is an intermediate form with both necrotic and apoptotic features. The efficient coupling of TNF receptors to a caspase-independent death event in an epithelial cell suggests an alternative approach to cancer therapy.

    Topics: Active Transport, Cell Nucleus; Adenocarcinoma; Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Caspase Inhibitors; Caspases; Colorectal Neoplasms; Enzyme Inhibitors; Epithelial Cells; fas Receptor; Humans; Lymphotoxin beta Receptor; Mice; Microscopy, Electron; Mitochondria; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; Tumor Cells, Cultured; TWEAK Receptor

2002
The activity of caspase-3-like proteases is elevated during the development of colorectal carcinoma.
    Cancer letters, 1999, Aug-23, Volume: 143, Issue:1

    Activated caspase-3-like proteases promote apoptotic cell death by cleaving cellular substrates. Caspase-3-like activity was measured in colonic carcinomas and in matched normal colonic mucosa from 31 patients and was significantly elevated in 25/ 31 colonic carcinomas and adenomas when compared to normal mucosa (P < 0.0001). Caspase-3-like activity was much higher in normal mucosa and tumours of female subjects than of males (P < 0.0001). No correlation was obtained between caspase-3-like activity and location of the tumour, tumour grade, stage, or patient age. The marked increase in caspase-3-like activity in colorectal carcinomas may reflect an increase in the proportion of cells undergoing spontaneous apoptosis.

    Topics: Adenoma; Adult; Aged; Aged, 80 and over; Amino Acid Chloromethyl Ketones; Apoptosis; Carcinoma; Caspase 3; Caspase Inhibitors; Caspases; Colorectal Neoplasms; Coumarins; Cysteine Proteinase Inhibitors; Enzyme Precursors; Female; Humans; Intestinal Mucosa; Jurkat Cells; Male; Middle Aged; Oligopeptides

1999