stilbenes and Lymphoma--Large-B-Cell--Diffuse
stilbenes has been researched along with Lymphoma--Large-B-Cell--Diffuse* in 6 studies
Other Studies
6 other study(ies) available for stilbenes and Lymphoma--Large-B-Cell--Diffuse
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Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells.
Diffuse large B-cell lymphoma (DLBCL) is the most common category and disease entity of non-Hodgkin lymphoma. Osalmide and pterostilbene are natural products with anticancer activities via different mechanism. In this study, using a new synthetic strategy for the two natural products, we obtained the compound DCZ0801, which was previously found to have anti-multiple myeloma activity. We performed both in vitro and in vivo assays to investigate its bioactivity and explore its underlying mechanism against DLBCL cells. The results showed that DCZ0801 treatment gave rise to a dose- and time-dependent inhibition of cell viability as determined by CCK-8 assay and flow cytometry assay. Western blot analysis results showed that the expression of caspase-3, caspase-8, caspase-9 and Bax was increased, while BCL-2 and BCL-XL levels were decreased, which suggested that DCZ0801 inhibited cell proliferation and promoted intrinsic apoptosis. In addition, DCZ0801 induced G0/G1 phase arrest by downregulating the protein expression levels of CDK4, CDK6 and cyclin D1. Furthermore, DCZ0801 exerted an anti-tumor effect by down-regulating the expressions of p-PI3K and p-AKT. There also existed a trend that the expression of p-JNK and p-P38 was restrained. Intraperitoneal injection of DCZ0801 suppressed tumor development in xenograft mouse models. The preliminary metabolic study showed that DCZ0801 displayed a rapid metabolism within 30 min. These results demonstrated that DCZ0801 may be a new potential anti-DLBCL agent in DLBCL therapy. Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle Checkpoints; Cell Line, Tumor; Cyclophosphamide; Cytotoxins; Lymphoma, Large B-Cell, Diffuse; Salicylanilides; Stilbenes | 2020 |
Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma cells.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Pterostilbene, a natural dimethylated analog of resveratrol, has been shown to possess diverse pharmacological activities, including anti-inflammatory, antioxidant and anticancer properties. However, to the best of our knowledge, there has been no study of the effects of pterostilbene upon hematological malignancies. Herein, we report the antitumor activity and mechanism of pterostilbene against DLBCL cells both in vitro and in vivo. We found that pterostilbene treatment resulted in a dose-dependent inhibition of cell viability. In addition, pterostilbene exhibited a strong cytotoxic effect, as evidenced not only by reductions of mitochondrial membrane potential (MMP) but also by increases in cellular apoptotic index and reactive oxygen species (ROS) levels, leading to arrest in the S-phase of the cell cycle. Furthermore, pterostilbene treatment directly up-regulated p-p38MAPK and down-regulated p-ERK1/2. In vivo, intravenous administration of pterostilbene inhibited tumor development in xenograft mouse models. Overall, the results suggested that pterostilbene is a potential anti-cancer pharmaceutical against human DLBCL by a mechanism involving the suppression of ERK1/2 and activation of p38MAPK signaling pathways. Topics: Animals; Apoptosis; Caspases; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Humans; Lymphoma, Large B-Cell, Diffuse; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Mice, Inbred BALB C; Mice, Nude; Reactive Oxygen Species; Stilbenes; Xenograft Model Antitumor Assays | 2016 |
Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis.. We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect.. Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway. Topics: Apoptosis; Cell Line, Tumor; Cell Survival; Cytochromes c; Humans; Immunoblotting; Lymphoma, Large B-Cell, Diffuse; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes | 2011 |
Prognostic significance of BAD and AIF apoptotic pathways in diffuse large B-cell lymphoma.
To determine whether proapoptotic proteins were associated with clinicopathologic heterogeneity and influenced survival in patients with diffuse large B-cell lymphoma (DLBCL), we evaluated patterns of expression of the BCL-2 family member BAD, PP1alpha (the catalytic subunit of PP1 involved in activation of BAD), and apoptosis-inducing factor (AIF).. We retrospectively analyzed 46 patients all treated with standard chemotherapy ([CHOP] cyclophosphamide/doxorubicin/vincristine/prednisone-like); of these, 16 received rituximab. Immunohistochemical analyses were performed from biopsy samples of nodal DLBCL that were performed at initial diagnosis. Normal reactive lymph nodes were used as controls.. BAD expression was found in 38 of 46 DLBCL cases and, though variable, was often strong. PP1alpha and AIF were detected in all tumors tested with a relative strong expression. Lower BAD expression was shown to be significantly associated with advanced clinical stages (Ann Arbor stage III + IV and International Prognostic Index intermediate-high to high; P = .006 and P = .0008, respectively). Moreover, BAD staining was positively correlated with BCL-2 (P = .022) and PP1alpha (P = .013) staining. Finally, high AIF expression proved to be predictive of a longer overall survival in non-rituximab-treated patients.. Our study shows for the first time in DLBCL that differential BAD expression might play a role in the development of the disease, possibly reflecting its function as a tumor suppressor. Furthermore, our data highlight the interest in targeting BAD phosphatases and AIF-mediated mitochondrial apoptosis for new therapeutic strategies. Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Inducing Factor; B-Lymphocytes; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Prognosis; Rituximab; Stilbenes; Vincristine | 2010 |
Inhibition of phosphatidylinositol 3-kinase-mediated glucose metabolism coincides with resveratrol-induced cell cycle arrest in human diffuse large B-cell lymphomas.
An abnormally high rate of aerobic glycolysis is characteristic of many transformed cells. Here we report the polyphenolic compound, resveratrol, inhibited phosphatidylinositol 3-kinase (PI-3K) signaling and glucose metabolism, coinciding with cell-cycle arrest, in germinal center (GC)-like LY1 and LY18 human diffuse large B-cell lymphomas (DLBCLs). Specifically, resveratrol inhibited the phosphorylation of Akt, p70 S6K, and S6 ribosomal protein on activation residues. Biochemical analyses and nuclear magnetic resonance spectroscopy identified glycolysis as the primary glucose catabolic pathway in LY18 cells. Treatment with the glycolytic inhibitor 2-deoxy-D-glucose, resulted in accumulation of LY18 cells in G0/G1 -phase, underscoring the biological significance of glycolysis in growth. Glycolytic flux was inhibited by the PI-3K inhibitor LY294002, suggesting a requirement for PI-3K activity in glucose catabolism. Importantly, resveratrol treatment resulted in inhibition of glycolysis. Decreased glycolytic flux corresponded to a parallel reduction in the expression of several mRNAs encoding rate-limiting glycolytic enzymes. These results are the first to identify as a mechanism underlying resveratrol-induced growth arrest, the inhibition of glucose catabolism by the glycolytic pathway. Taken together, these results raise the possibility that inhibition of signaling and metabolic pathways that control glycolysis might be effective in therapy of DLBCLs. Topics: Antineoplastic Agents, Phytogenic; Cell Cycle; Cell Line, Tumor; Chromones; Enzyme Inhibitors; Glucose; Glycolysis; Humans; Lymphoma, Large B-Cell, Diffuse; Morpholines; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Resveratrol; Stilbenes | 2006 |
Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation.
The synthesis and structure-activity relationship study of a series of compounds with heterocycles in place of the cis double bond in combretastatin A-4 (CA-4) are described. Substituted tosylmethyl isocyanides were found to be the key intermediates in construction of the heterocycles. Cytotoxicities of the heterocycle-based CA-4 analogues were evaluated against NCI-H460 and HCT-15 cancer cell lines. 3-Amino-4-methoxyphenyl and N-methyl-indol-5-yl were the best replacements for the 3-hydroxy-4-methoxyphenyl in CA-4. 4,5-Disubstituted imidazole was found to be the best for the replacement of the cis double bond in CA-4. Medicinal chemistry efforts led to the discovery of compounds 24h and 25f that were found to be 32 and 82% bioavailable, respectively, in rat. Evaluation of 24h and 25f against murine M5076 reticulum sarcoma in mice revealed that both compounds were orally efficacious with an increase in life span of 38.5 and 40.5%, respectively. Topics: Administration, Oral; Animals; Antineoplastic Agents; Biopolymers; Cell Division; Dogs; Drug Screening Assays, Antitumor; Haplorhini; Humans; Imidazoles; Lymphoma, Large B-Cell, Diffuse; Mice; Mice, Nude; Neoplasm Transplantation; Rats; Stilbenes; Structure-Activity Relationship; Transplantation, Heterologous; Tubulin; Tumor Cells, Cultured | 2002 |