OBJECTIVE: To investigate the effects and molecular mechanisms of 2-12alkyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD) on diffuse large B lymphoma (DLBCL). METHODS: In animal experiments, 4-week-aged BALB/C mice were divided into 5 groups, 20 mice in each group. Mice were inguinal injected with DLBCL cell line OCI-LY19 cells 0.1 ml at the concention of 1 × 10 /ml. Two days later, mice were treated with DMDD at the doses of 0, 1, 5, 25 and 125 mg/kg by intragastric administration respectively, once /2 days. Ten mice of each group were killed on the 18th day of administration, and the tumor tissues were weighed. The survival time of the remaining mice were recorded. In cell experiments, OCI-LY19 cells were added to 96-well culture plates, 100 μl 1×10 cells/ml per well, then 100 μl DMDD was added to the well and the final concentrations were 0, 1, 5, 25 and 125 μmol/L respectively. The cells were treated with DMDD for 0, 24, 48 and 72 h, three wells in each group. The cell proliferation activity was detected by MTS assay. According to the results of cell proliferation experiments, OCI-LY19 cells were treated with DMDD at the concentrations of 0 μmol/L, 5 μmol/L and 25 μmol/L for 24 h. The apoptosis rate was analyzed by flow cytometry, the nuclear type was observed by hoechst staining, the mitochondrial membrane potential was observed by JC-1 staining, cytotoxicity of drugs was evaluated by LDH release experiment, gene expression and transcription were analyzed by qPCR and Western blot. RESULTS: Compared with 0 mg/kg drug group, DMDD at the dose of 1～125 mg/kg could inhibit the growth of tumor tissue in mice and prolong their survival time (P＜0.01). Cell experiments showed: in DMDD group, the proliferation activity of OCI-LY19 cells was decreased significantly and the level of apoptosis was increased significantly (P＜0.01), nuclear fragmentation, agglutination, apoptotic bodies occurred and mitochondrial membrane potential was decreased, the LDH release rate was increased significantly (P＜0.01), the expressions of caspase-3 and bax genes and the phosphorylation level of Ikappa B alpha in cells were up-regulated significantly, the protein expression levels of bcl-2, bcl-xL, jak2 and stat3 were inhibited significantly (P＜0.01). CONCLUSION DMDD can inhibit the expressions of JAK2, STAT3 and p-Ikappa B alpha in JAK2/STAT3 and NF-kappa B signal pathways, down-regulate BCL-2/BAX and activate Caspase-3, finally, activate the endogenous pathway of mitochondrial apoptosis in OCI-LY19 cells and promote the apoptosis of DLBCL cells, inhibit proliferation of OCI-LY19 cells. It has inhibitive effects on DLBCL.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cyclohexenes ; pharmacology ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; pathology ; Mice ; Mice, Inbred BALB C ; Signal Transduction ; drug effects

OBJECTIVE: To investigate the effects of tectochrysin on prostate cancer cell line 22Rv.1 and reveal its molecular mechanism. METHODS: Tectochrysin at the concentrations of 0～20 μg/ml was applied to 22Rv.1 cells and normal prostate cell RWPE-1. The proliferation activity of the cells was detected by MTS assay. Flow cytometry and hoechst 33342 staining were used to analyze the effects of drugs on cell apoptosis, death, cell cycle and nuclear type changes. LDH release test was used to analyze the cytotoxicity of the drug to 22Rv.1 cells. QPCR and Western blot were used to analyze the effects of the drug on the expressions of genes in 22Rv.1 cells. Finally, the tumor inhibited effect of the drug on the bearing tumor BALB/c mice were confirmed though anti-tumor experiment. RESULTS: Tectochrysin could significantly inhibit the proliferation activity of 22Rv.1 cells and induced their apoptosis, and promoted the expressions of genes dr4, dr5, trail, p53, caspase-3, caspase-8, caspase-9, bid, bax and foxo3, inhibited the expressions of anti-apoptotic genes akt, pi3k and bcl-2. CONCLUSION Tectochrysin can induce prostate cancer cells apoptosis through affecting TRAIL and PI3K/AKT signaling pathways, and has anti-prostate cancer effect.
Animals ; Apoptosis ; Cell Line, Tumor ; Flavonoids ; pharmacology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Prostatic Neoplasms ; drug therapy ; pathology ; Signal Transduction ; TNF-Related Apoptosis-Inducing Ligand ; metabolism

OBJECTIVE: To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms. METHODS: Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18 day since first Birinapant injection, 10 mice were killed in each group to weigh tumor tissue and survival time was recorded from the remaining 10 mice.The effects of Birinapant on the growth of the tumor and the survival time of tumor-bearing mice were observed. RESULTS: Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (<0.01).The cell mitochondrial membrane potential was decreased and the karyotype was changed (<0.01).At the same time, the transcription and expression levels of genes cellular inhibitor of apoptosis protein 1(cIAP-1), cellular inhibitor of apoptosis protein 2(cIAP-2), ras, raf, mek and erk were significantly decreased (<0.01), while the expression levels of caspase-3 and caspase-9 genes were up-regulated (<0.01).Compared with the model group (MG), the growth of the tumor was inhibited significantly and the survival time of the tumor-bearing mice was prolonged after Birinapant treatment (<0.01). CONCLUSIONS Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Dipeptides ; Humans ; Indoles ; Liver Neoplasms ; Male ; Mice ; Mice, Inbred BALB C ; Mitochondrial Proteins

Apoptosis ; Breast Neoplasms/drug therapy* ; Caspases ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Mitochondria ; Oligopeptides