Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, have potential therapeutic activity in tumor therapy. However, the therapeutic effect in solid tumor treatment with CTX III are still largely unknown. In the present study, we investigated whether CTX III affects cell growth and cell cycle progression of hepatocellular carcinoma cell (HepG2). We found that the proliferation of HepG2 cell was inhibited by CTX III, to some extent, in a time- and dose-dependent manner (IC50 2.58microg/ml at 24h). Flow cytometric analysis and annexin V labeling also demonstrated that CTX III increased the percentage of apoptotic cells being associated with cell cycle arrest at S-phase. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot revealed that cyclin D1, cyclin A and cyclin E, which involved in cell apopotosis and cell cycle progression, were down regulated both at transcription and translation levels. CTX III-induced caspase-8, -9 and caspase-3 activation, generation of truncated Bid, releasing of cytochrome c and the change of Bcl-2/Bax ratio on protein and mRNA levels. These findings demonstrated that cyclin D1, cyclin B and cyclin A down-regulation, change of Bcl-2/Bax ratio and caspase-8 and -9 activation contribute to CTX III-induced HepG2 cell apoptosis.
 ...
PMID:Apoptosis of human hepatocellular carcinoma cell (HepG2) induced by cardiotoxin III through S-phase arrest. 1898 2

In this study, we investigated the effects of DADS on human colon cancer cell line COLO 205 on cell cycle arrest and apoptosis in vitro. After 24 h treatment of COLO 205 cells with DADS, the dose- and time-dependent decreases of viable cells were observed and the IC50 was 22.47 microM. The decreased percentages of viable cells are associated with the production of ROS. Treatment of COLO 205 cells with DADS resulted in G2/M phase arrest and apoptosis occurrence through the mitochondrial-pathway (Bcl-2, Bcl-xL down-regulation and Bak, Bax up-regulation). DADS increased cyclin B, cdc25c-ser-216-9 and Wee1 but did not affect CDK1 protein and gene expression within 24 h of treatment. DADS-induced apoptosis was examined and confirmed by DAPI staining and DNA fragmentation assay. DADS promoted caspase-3, -8 and -9 activity and induced apoptosis were accompanied by increasing the levels of Fas, phospho-Ask1 and -JNK, p53 and decreasing the mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-9 and -3. The COLO 205 cells were pre-treated with JNK inhibitor before leading to decrease the percentage of apoptosis which was induced by DADS. Inhibition of caspase-3 activation blocked DADS-induced apoptosis on COLO 205 cells.
 ...
PMID:Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways. 1903 4

Arsenic compounds have been used as anti-cancer agents in traditional Chinese medicine. Ionizing radiation (IR) is one of the most effective tools in the clinical treatment of cancer. The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. A combination of different anti-tumoral treatment modalities is advantageous in limiting non-specific toxicity often observed by an exceedingly high dose of single regimen. The present study aimed at investigating the enhanced effects and mechanisms in cell cycle distribution and apoptosis of U937 cells, a human pre-monocytic leukemia cell line lacking functional p53 protein, after combination treatment with irradiation and As(2)O(3). Our results indicated that combined treatment led to activation of cdc-2, which is related to the expression of cyclin B. In addition, combined treatment increased apoptotic cell death in U937 cells, which is correlated with the induction of mitotic arrest, the increase in intracellular reactive oxygen species (ROS) generation, the decrease in B-cell leukemia/lymphoma 2 (Bcl-2) and B-cell leukemia/lymphoma XL (Bcl-XL) levels, the loss of mitochondria membrane potential, and the activation of caspase-3. We found that combining radiation and As(2)O(3) may be an effective strategy against p53-deficient leukemia cells.
 ...
PMID:Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation. 1915 21

Berberine, an alkaloid, has anti-tumor properties in some cancer cells, but action mechanisms are not clear yet. We here investigated the anticancer activity of berberine and possible mechanisms in human neuroblastoma SK-N-SH and SK-N-MC cells. The p53-expressing cells, SK-N-SH (IC50=37 microM) were more susceptible to berberine than the p53-deficient cells, SK-N-MC (IC50 > or =100 microM) without cytotoxic effect on the cortical neuronal cells. Berberine caused cell cycle arrest in G0/G1 phase and apoptotic cell death, and these effects were much greater in SK-N-SH cells than those in SK-N-MC cells. Berberine much greatly decreased G0/G1 phase-associated cyclin and cyclin-dependent kinase (cyclin D1, cyclin E, Cdk2, and Cdk4) expression, and increased apoptotic gene expression and activation of caspase-3 in SK-N-SH cells. Exploration of p53 siRNA or pifithrin-alpha (PFT-alpha), a p53 inhibitor, in the SK-N-SH cells resulted in increase of IC50 values for cell viability, and decreased apoptotic cell death, expression of p53 and activation of caspase-3. Therefore, these results showed that berberine causes p53-dependent apoptotic death of neuroblastoma cells, and suggested that berberine may be useful as an anticancer agent for neuroblastoma.
 ...
PMID:Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis. 1918 64

Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferation in the skin of Swiss albino mice. Lupeol treatment showed significant (p < 0.05) preventive effects with marked inhibition at 48, 72, and 96 h against DMBA-mediated neoplastic events. Cell-cycle analysis showed that lupeol-induced G2/M-phase arrest (16-37%) until 72 h, and these inhibitory effects were mediated through inhibition of the cyclin-B-regulated signaling pathway involving p53, p21/WAF1, cdc25C, cdc2, and cyclin-B gene expression. Further lupeol-induced apoptosis was observed, as shown by an increased sub-G1 peak (28%) at 96 h, with upregulation of bax and caspase-3 genes and downregulation of anti-apoptotic bcl-2 and survivin genes. Thus, our results indicate that lupeol has novel anti-proliferative and apoptotic potential that may be helpful in designing strategies to fight skin cancer.
 ...
PMID:Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin. 1923 20

Inhibitors of cyclin-dependent kinases (CDKs) undergoing clinical trials as anticancer agents usually target several CDKs in cells. Some of them are also able to increase cellular levels of p53 protein and to activate p53-regulated transcription. To define the role of p53 in the anticancer effect of selective CDK inhibitors, two related compounds roscovitine and olomoucine II were studied. Roscovitine differs functionally from its congener olomoucine II only in the selectivity towards transcriptional CDK9. Action of both compounds on proliferation, cell-cycle progression, and apoptosis was examined in RPMI-8226 cells expressing the temperature-sensitive mutant of p53 and in MCF-7 cells with wild-type p53. Both compounds blocked proliferation, decreased phosphorylation of RNA polymerase II, downregulated antiapoptotic protein Mcl-1 in both cell lines in a dose-dependent manner, and also activated p53 in MCF-7 cells. Moreover, we showed that the anticancer efficiency of CDK inhibitors was enhanced by active p53 in RPMI-8226 cells kept at permissive temperature, where downregulation of Mcl-1, fragmentation of PARP-1, and increased caspase-3 activity was detected with lower doses of the compounds. The results confirm that functional p53 protein may enhance the anticancer activity of roscovitine that could be beneficial for anticancer therapy.
 ...
PMID:Functional p53 in cells contributes to the anticancer effect of the cyclin-dependent kinase inhibitor roscovitine. 1930 36

Shi-Liu-Wei-Liu-Qi-Yin (SLWLQY) was traditionally used to treat cancers. However, scientific evidence of the anticancer effects still remains undefined. In this study, we aimed to clarify the possible mechanisms of SLWLQY in treating cancer. We evaluated the effects of SLWLQY on apoptosis-related experiments inducing in TSGH-8301 cells by (i) 3-(4,5-dimethylthiazol-zyl)-2,5-diphenylterazolium bromide (MTT) for cytotoxicity; (ii) cell-cycle analysis and (iii) western blot analysis of the G2/M-phase and apoptosis regulatory proteins. Human bladder carcinoma TSGH-8301 cells were transplanted into BALB/c nude mice as a tumor model for evaluating the antitumor effect of SLWLQY. Treatment of SLWLQY resulted in the G2/M phase arrest and apoptotic death in a dose-dependent manner, accompanied by a decrease in cyclin-dependent kinases (cdc2) and cyclins (cyclin B1). SLWLQY stimulated increases in the protein expression of Fas and FasL, and induced the cleavage of caspase-3, caspase-9 and caspase-8. The ratio of Bax/Bcl(2) was increased by SLWLQY treatment. SLWLQY markedly reduced tumor size in TSGH-8301 cells-xenografted tumor tissues. In the tissue specimen, SLWLQY up-regulated the expression of Fas, FasL and Bax proteins, and down-regulated Bcl(2) as well as in in vitro assay. Our results showed that SLWLQY reduced tumor growth, caused cell-cycle arrest and apoptosis in TSGH-8301 cells via the Fas and mitochondrial pathway.
 ...
PMID:Aqueous Extract of Shi-Liu-Wei-Liu-Qi-Yin Induces G2/M Phase Arrest and Apoptosis in Human Bladder Carcinoma Cells via Fas and Mitochondrial Pathway. 1938 39

The cytotoxicity of berberine on C6 rat glioma cells indicated that berberine induced morphological changes and caused cell death through G2/M arrest and apoptosis. While undergoing apoptosis, there was a remarkable accumulation of G2/M cells with the upregulatoin of Wee1 but it also inhibited cyclin B, CDK1 and Cdc25c that led to G2/M arrest. Along with cytotoxicity in C6 cells, several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3 and -8 and DNA fragmentation were induced. Berberine increased the levels of GADD153 and GRP 78 in C6 cells based on the examination of Western blotting and this is a major hallmark of endoplasmic reticulum (ER) stress. We also found that berberine promoted the production of reactive oxygen species and Ca2+ in C6 cells. Western blotting assay also showed that berberine inhibited the levels of anti-apoptotic protein Bcl-2 but increased the levels of pro-apoptotic protein Bax before leading to a decrease in the levels of mitochondrial membrane potential (DeltaPsim) followed by cytochrome c release that caused the activations of capase-9 and -3 for apoptotic occurrence. The caspase-8, -9 and -3 were activated by berberine in C6 cells based on the substrate solution (PhiPhiLux-G1D1, CaspaLux 8-L1D2, CaspaLux 9-M1D2 for caspase-3, -8 and -9, respectively) and analyzed by flow cytometer and each inhibitor of caspase-8, -9 and -3 led to increase the percentage of viable C6 cells after exposure to berberine. This finding was also confirmed by Western blot assay which showed that berberine promoted the active form of caspase-8, -9 and -3. These results demonstrate that the cytotoxicity of berberine in C6 rat glioma cells is attributable to apoptosis mainly through induced G2/M-arrested cells, in an ER-dependent manner, via a mitochondria-dependent caspase pathway regulated by Bax and Bcl-2.
 ...
PMID:Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells. 1942 87

Our goals were to examine the dual-directional regulation effects of resveratrol (1) in vitro by using MCF-7 cells (estradiol receptor-positive cells), study its mechanism of action, and give a systematical analysis of the regulatory networks of each related factor. An MTT test and growth curve showed that the proliferation of MCF-7 cells was inhibited by a high concentration of 1, and that its IC(50) was 8.70 x 10(-5) +/- 0.23 mol/l. However, 1 induced the proliferation of MCF-7 cells at 10(-7)-10(-5) mol/l, and resulted in a peak proliferation at 1.0 x 10(-7) mol/l. A high concentration of 1 arrested cell cycle progression at the G(1) phase, and a typical "sub-G(1) peak" of apoptotic cells was also observed by flow cytometry. The proliferation index of MCF-7 cells increased significantly with a low concentration of 1 (p < 0.05). 1 in high concentrations induced Bax, caspase-3, and cyclin-dependent kinase (CDK) inhibitor P21 expression, whereas the expressions of cyclin CDK2, Bcl-2, and proliferating cell nuclear antigen (PCNA) were decreased by 1 treatment. Conversely, treatment with low concentrations of 1 decreased the expression of P21 and Bax, while the expressions of cyclin CDK2, Bcl-2, and PCNA were increased. These results suggest that 1 had a dual-regulatory effect on MCF-7 cells. CDK-associated protein was a key factor at both the high and low concentrations used in this study.
 ...
PMID:Effect of proliferation, cell cycle, and Bcl-2s of MCF-7 cells by resveratrol. 1943 Oct 20

Because DNA methyltransferase (DNMT) inhibitors like azacytidine and decitabine are known to be effective in the clinic for diseases like myelodysplastic syndromes that may result in part from transcriptional dysregulation due to epigenetic changes, there is interest in developing novel DNMT inhibitors that would be more effective and less toxic. The effects of one such agent, zebularine, which inhibits DNMT and cytidine deaminase, were assessed in two human breast cancer cell lines, MDA-MB-231 and MCF-7. Zebularine treatment inhibited cell growth in a dose and time dependent manner with an IC-50 of approximately 100 microM and 150 microM in MDA-MB-231 and MCF-7 cells, respectively, on 96 h exposure. This was associated with increased expression of p21, decreased expression of cyclin-D, and induction of S-phase arrest. At high doses zebularine induced changes in apoptotic proteins in a cell line specific manner manifested by alteration in caspase-3, Bax, Bcl2 and PARP cleavage. Like other DNMT inhibitors, zebularine decreased expression of DNMTs post-transcriptionally as well as expression of other epigenetic regulators like methyl CpG binding proteins and global acetyl H3 and H4 protein levels. Its capacity to reexpress epigenetically silenced genes in human breast cancer cells at low doses was confirmed by its ability to induce expression of estrogen and progesterone receptor mRNA in association with changes suggestive of active chromatin at the ER promoter as evidenced by ChIP. Finally, its effect in combination with other DNMT or HDAC inhibitors like decitabine or vorinostat was explored. The combination of 50 muM zebularine with decitabine or vorinostat significantly inhibited cell proliferation and colony formation in MDA-MB-231 cells compared with either drug alone. These findings suggest that zebularine is an effective DNMT inhibitor and demethylating agent in human breast cancer cell lines and potentiates the effects of other epigenetic therapeutics like decitabine and vorinostat.
 ...
PMID:Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. 1945 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>