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

benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone has been researched along with Endometrial-Neoplasms* in 4 studies

Other Studies

4 other study(ies) available for benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Endometrial-Neoplasms

ArticleYear
BF175 inhibits endometrial carcinoma through SREBP-regulated metabolic pathways in vitro.
    Molecular and cellular endocrinology, 2021, 03-01, Volume: 523

    Elevated lipogenesis is an important metabolic hallmark of rapidly proliferating tumor such as endometrial carcinoma (EC). The sterol regulatory element-binding protein 1 (SREBP1) is a master regulator of lipogenesis and involved in EC proliferation. BF175 is a novel chemical inhibitor of SREBP pathway, and has shown potent anti-lipogenic effects. However, the effect of BF175 on EC cells are yet to be determined. In the present study, we found that BF175 decreased cell viability, colony formation and migratory capacity, inducing autophagy and mitochondrial related apoptosis in EC cell line AN3CA. Z-VAD-FMK partially attenuated the effect of BF175 on AN3CA. In addition, BF175 significantly downregulated SREBPs and their downstream genes. The levels of free fatty acids and total cholesterol were also inhibited. Microarray analysis suggested BF175 treatment obviously affected lipid metabolic pathways in EC. Taken together, we validated BF175 exhibited anti-tumor activity by targeting SREBP-dependent lipogenesis and inducing apoptosis which mitochondrial pathway involved in, suggesting that it's potential as a novel therapeutic reagent for EC.

    Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Autophagy; Boron Compounds; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Cholesterol; Down-Regulation; Endometrial Neoplasms; Fatty Acids; Female; Gene Expression Profiling; HEK293 Cells; Humans; Lipogenesis; Membrane Potential, Mitochondrial; Metabolic Networks and Pathways; Mitochondria; Sterol Regulatory Element Binding Protein 1; Transcription, Genetic; Tumor Stem Cell Assay

2021
Triptolide induces apoptosis in endometrial cancer via a p53‑independent mitochondrial pathway.
    Molecular medicine reports, 2014, Volume: 9, Issue:1

    Triptolide (TP), the primary active component purified from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F (TWHF), has been shown to possess antitumor activity in several types of solid tumors. In the present study, we investigated the antitumor effect of TP in human endometrial cancer cells (HEC-1B) and elucidated its possible underlying mechanisms. HEC-1B cells were treated with various doses of TP (10, 20, 40, 80, 160 and 320 nM), and the cell viability was assessed by Cell Counting Kit-8 (CCK-8) and flow cytometric analysis. Results indicated that TP inhibited the proliferation of HEC-1B cells in a dose- and time‑dependent manner. To further investigate its mechanisms, the levels of apoptosis and the changes in caspase-3/9 expression in HEC-1B cells by pretreatment with z-VAD-fmk, a pan-caspase inhibitor, were detected by CCK-8 and western blotting. The cytotoxic effects of TP were significantly inhibited by z-VAD‑fmk. At the molecular level, TP did not effectively activate the p53 signaling pathway, but upregulated caspase-3/9 and downregulated bcl-2 without changing the bax level. Our studies revealed that TP has an effect on the apoptotic ability of endometrial cancer cells via a p53-independent mitochondrial pathway, presenting a novel strategy to evade drug resistance in tumorigenesis. The ability of TP to be a potential chemotherapeutic agent for endometrial cancer should be considered.

    Topics: Amino Acid Chloromethyl Ketones; Antineoplastic Agents, Alkylating; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Cell Line, Tumor; Diterpenes; Down-Regulation; Endometrial Neoplasms; Epoxy Compounds; Female; Humans; Mitochondria; Phenanthrenes; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Tumor Suppressor Protein p53; Up-Regulation

2014
Tubulin inhibitor AEZS 112 inhibits the growth of experimental human ovarian and endometrial cancers irrespective of caspase inhibition.
    Oncology reports, 2009, Volume: 22, Issue:2

    AEZS 112 is an orally active small molecule anticancer drug which inhibits the polymerization of tubulin at low micromolar concentrations. The current study investigates the anti-tumor effect and the mechanism of action of AEZS 112 in in vitro models of human ovarian and endometrial cancers. Four human ovarian and 2 endometrial cancer cell lines were incubated with increasing concentrations of AEZS 112 with and without multi-caspase inhibitor zVAD-FMK for 72 hours. Cytotoxic effects of AEZS 112 were analyzed using crystal violet staining, FACS analysis of DNA content as well as Annexin V/propidium iodide-double staining. AEZS 112 displayed anti-tumor activity in all six cell lines. The EC50 determined after 72-h incubation for Ishikawa and HEC 1A was 0.0312 and 0.125 microm, respectively. The EC50 was 5 microm for SKOV 3 cells, 1 microm for 0.5 microm for OAW 42 cells, 0.125 microm for OvW 1 cells and 0.0312 microm for PA 1 cells. Cytotoxic effects of AEZS 112 could not be abrogated by caspase inhibition with pan-caspase inhibitor zVAD-fmk. Annexin V/propidium iodide-double staining after treatment with AEZS 112 was indicative of necrosis-like cell death. AEZS 112 dose-dependently increased non-vital hypodiploid cells and the cytotoxic effect was least pronounced in G2 phase of the cell cycle, indicating cell death during mitosis, as determined by FACS analysis. The orally active small molecule tubulin inhibitor AEZS 112 showed anti-tumor activity in human ovarian and endometrial cancer cell lines at low micromolar concentrations, which could not be abrogated by caspase inhibition and is therefore a good candidate for in vivo studies in these tumors.

    Topics: Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Caspase Inhibitors; Cell Cycle; Cell Line, Tumor; Endometrial Neoplasms; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerases; Tubulin Modulators

2009
Caspase cascade of Fas-mediated apoptosis in human normal endometrium and endometrial carcinoma cells.
    Molecular human reproduction, 2006, Volume: 12, Issue:9

    Human endometrial epithelial cells undergo apoptosis immediately before the menstrual period. Apoptotic signalling was analysed using human endometrial tissue and a human endometrial carcinoma cell line (HHUA). Activity levels of caspase-3, -8, and -9 were elevated in human endometrium during the late secretory phase and in HHUA cells incubated with an anti-Fas monoclonal antibody (mAb). Fas-mediated apoptosis of HHUA cells was blocked by prior exposure to inhibitors of caspase-9, -8 and -3. In HHUA cells treated with anti-Fas mAb, a release of cytochrome c was detected in the cytosolic fraction, in addition a full-length Bid was degraded. Full-length FLIP(L) (p55) was degraded during apoptosis, and p29 (regarded as the product of p55 cleavage) appeared instead of FLIP(L). In normal human endometrial tissue, Bid degradation was also observed in a cyclic manner with a peak during the early secretory phase of the menstrual cycle. Furthermore, the release of cytochrome c was seen in the early secretory phase. However, expression of FLIP(S) was only observed during the menstrual cycle in normal endometrial tissue. We concluded that the main apoptotic signalling in both normal human endometrial tissue and HHUA cells exposed to anti-Fas mAb is the mitochondrial pathway via Bid degradation. Although the function of FLIP is still unknown on normal endometrial tissue, it may be regulated by FLIP(L) expression on HHUA cells derived from human endometrial carcinoma.

    Topics: Adult; Amino Acid Chloromethyl Ketones; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Apoptosis; BH3 Interacting Domain Death Agonist Protein; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase Inhibitors; Caspases; Cell Line, Tumor; Cell Proliferation; Cysteine Proteinase Inhibitors; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; Endometrial Neoplasms; Endometrium; Epithelial Cells; Estradiol; fas Receptor; Female; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Menstrual Cycle; Middle Aged; Progesterone; Receptors, Tumor Necrosis Factor; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Time Factors

2006