Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the present study was to investigate the effect of aqueous extract from the root of Platycodon grandiflorum (AEPG) on the cell growth and apoptosis in human lung carcinoma cell line A549. Exposure of A549 cells to AEPG resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. This increase in apoptosis was associated with a decrease in Bcl-2 expression, an increase of Bax and an activation of caspase-3. AEPG treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by AEPG treatment. These findings suggest that the apoptotic events by AEPG were associated with the diminished telomerase activity and down-regulation of Bcl-2 expression.
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PMID:Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandiflorum in human lung carcinoma cells. 1574 58

The objective of the present study was to investigate the effect of beta-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae), on the cell growth and apoptosis in human lung carcinoma cell line A549. Exposure of A549 cells to beta-lapachone resulted in growth inhibition and induction of apoptosis in a time- and dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. This increase in apoptosis was associated with a decrease in Bcl-2 and expression, an increase of Bax, and an activation of caspase-3 and caspase-9. beta-lapachone treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the levels of human telomerase RNA (hTR) and c-myc expression were progressively down-regulated by beta-lapachone treatment. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of beta-lapachone.
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PMID:Growth inhibition of A549 human lung carcinoma cells by beta-lapachone through induction of apoptosis and inhibition of telomerase activity. 1575 97

Elderly lung cancer patients and those with poor performance status/co-morbid conditions are deprived of chemotherapy because of high toxicity of multidrug regimens. Human squamous cell lung carcinoma H520 cells treated with Curcumin were sensitized to the cytotoxicity caused by chemotherapeutic agent, Vinorelbine. Both caused apoptosis by increasing the protein expression of Bax and Bcl-xs while decreasing Bcl-2 and Bcl-X(L), releasing apoptogenic cytochrome c, and augmenting the activity of caspase-9 and caspase-3. Expression of Cox-2, NF-kappaB, and AP-1 was also affected. 23.7% apoptosis was induced in the H520 cells by treatment with Curcumin while Vinorelbine caused 38% apoptosis. Pre-treatment with Curcumin enhanced the Vinorelbine induced apoptosis to 61.3%. The findings suggest that Curcumin has the potential to act as an adjuvant chemotherapeutic agent and enhance chemotherapeutic efficacy of Vinorelbine in H520 cells in vitro. Thus, Curcumin offers the prospect of being beneficial in the above-mentioned patient groups.
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PMID:Curcumin enhances Vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway. 1588 9

6-(1-Hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) was reported to have cytotoxic activity against L1210 leukemia cells. In the present study, we investigated the apoptotic mechanism of DMNQ S-52 in vitro and in vivo in murine solid cancer cells. DMNQ S-52 exerted cytotoxicity against Lewis lung carcinoma (LLC) cells (IC50=12.3 microM). DMNQ S-52 increased Annexin V positive cell population in a concentration-dependent manner. DMNQ S-52 also induced apoptosis through caspase-mediated pathway, including activation of caspase-3, cleavage of Poly(ADP-ribose) polymerase (PARP) and decreased expression of Bcl-2 in LLC cells in a time and concentration-dependent fashion. DMNQ S-52 activated the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 as well as abrogated the expression of extracellular signal-regulated kinase (ERK) in a time-dependent manner at 10 microM. Similarly, cell proliferation inhibition by DMNQ S-52 was masked by caspase inhibitor Z-Asp-Glu-Val-Asp-fluoromethylketone (Z-VAD-FMK), JNK inhibitor SP600125 and p38 inhibitor SB203580, but not by MEK inhibitor U0126. Furthermore, i.p. administration of DMNQ S-52 at 5 mg/kg resulted in a potent inhibition of the growth of LLC cells implanted on the right flank of C57BL/6 mice compared to untreated control. Immunohistochemical analysis revealed the decreased tumor cell proliferation and increased tumor cell apoptosis in DMNQ S-52 treated tumor sections using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and proliferation cell nuclear antigen (PCNA). Taken together, these findings demonstrate that DMNQ S-52 may exhibit anti-tumor activity by inducing apoptosis via caspases and mitogen activated protein (MAP) kinase-dependent pathways.
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PMID:MAPK regulation and caspase activation are required in DMNQ S-52 induced apoptosis in Lewis lung carcinoma cells. 1589 20

Although histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. This study was undertaken to investigate the underlying mechanism of an HDAC inhibitor, Trichostatin A (TSA), -induced apoptosis in a human lung carcinoma cell line A549. The effects of this compound were also tested on cyclooxygenase (COX) activity. Treatment of A549 cells to TSA resulted in the inhibition of viability and the induction of apoptosis in a concentration-dependent manner, which could be proved by trypan blue counts, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. Apoptosis of A549 cells by TSA was associated with a down-regulation of anti-apoptotic Bcl-2 protein and an up-regulation of pro-apoptotic Bax protein. TSA treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant degradation of poly(ADP-ribose)-polymerase protein. Furthermore, TSA decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with an inhibition in prostaglandin E2 synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of TSA.
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PMID:Induction of apoptosis by trichostatin A, a histone deacetylase inhibitor, is associated with inhibition of cyclooxygenase-2 activity in human non-small cell lung cancer cells. 1601 Apr 30

Cantharidin isolated from Mylabris caraganae and other insects has been used as an anti-cancer drug in China for many years. However, its toxicity on the renal system and suppression effect on bone marrow limits its usage clinically. Based on the core structure of cantharidin, we have chemically synthesized two cantharidin analogues (compounds 2 and 3). The cytotoxic activity of these analogues was demonstrated on the Hep3B hepatocellular carcinoma, MDA-MB231 breast cancer, A549 non-small cell lung carcinoma and KG1a acute myelogenous leukaemia (AML) cell lines by monitoring the intracellular adenosine triphosphate level. Morphological changes in these cancer cell lines, including cell shrinkage and loss of adherent potential, were readily observed. By making use of the KG1a AML cells as a test model, we further found that mitochondrial membrane potential depolarization and reduction of intracellular bcl-2 anti-apoptotic protein level were involved. These resulted in the activation of caspase 3 protease activity and oligonucleosomal length DNA fragment formation as detected by both time resolved fluorescence technology-based caspase activity assay and TdT-mediated dUTP nick end-labelling assay.
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PMID:Induction of apoptosis on carcinoma cells by two synthetic cantharidin analogues. 1632 24

Lung cancer is one of the most common causes of cancer death worldwide. Although recent advances in chemotherapy and radiation therapy have yielded modest improvements in patient outcomes, overall survival remains poor. Therefore, new therapeutic targets are needed. Phosphoinositide-dependent kinase-1 (PDK1) is one potential target. The aim of the present studies was to investigate the potential of a celecoxib-derived PDK1 inhibitor (OSU03013), that does not inhibit cyclooxygenase-2, to kill lung cancer cells in vitro. Using human non-small-cell lung cancer A549 cells, OSU03013 dose-dependently induced apoptosis. After 6 h of treatment with 7.5 microM OSU03013, 26% of the cells were apoptotic, compared to 4% of the control cells as determined by measuring the sub-G1 peak of propidium iodide stained cells with flow cytometry. A similar increase in apoptosis was evident using the Cell Death ELISA assay. OSU03013-induced apoptosis was accompanied by a reduction in the mitochondrial membrane potential, the release of cytochrome c and the cleavage of caspase-3. Surprisingly, the phosphorylation of Akt at serine 473 was increased in A549 cells treated with 7.5 microM OSU03013. However, the toxicity of OSU03013 was reduced in A549 cells expressing a constitutively active form of Akt. These data demonstrate that OSU03013 induces apoptosis in A549 cells via the mitochondrial pathway. Inhibition of the Akt pathway appears uninvolved in this toxicity, although Akt can provide protection. These results also suggest the potential of celecoxib-derived agents to treat some forms of lung cancer.
Lung Cancer 2006 Apr
PMID:Cytotoxicity of a non-cyclooxygenase-2 inhibitory derivative of celecoxib in non-small-cell lung cancer A549 cells. 1649 9

Synthetic alkyl-lysophospholipids represent a family of promising anticancer drugs that induce apoptosis in a variety of tumor cells. Here we have found a differential subcellular distribution of the alkyl-lysophospholipid edelfosine in leukemic and solid tumor cells that leads to distinct anticancer responses. Edelfosine induced rapid apoptosis in human leukemic cells, including acute T-cell leukemia Jurkat and Peer cells, but promoted a late apoptotic response, preceded by G(2)/M arrest, in human solid tumor cells such as cervix epitheloid carcinoma HeLa cells and lung carcinoma A549 cells. c-Jun amino-terminal kinase (JNK) and caspase-3 were accordingly activated at earlier times in edelfosine-treated Jurkat cells as compared with drug-treated HeLa cells. Both leukemic and solid tumor cells took up this alkyl-lysophospholipid and expressed the two putative edelfosine targets, namely cell surface Fas death receptor (also known as APO-1 or CD95) and endoplasmic reticulum CTP: phosphocholine cytidylyltransferase. However, edelfosine was mainly located to plasma membrane lipid rafts in Jurkat and Peer leukemic cells and to endoplasmic reticulum in solid tumor HeLa and A549 cells. Edelfosine induced translocation of Fas, Fas-associated death domain-containing protein, and JNK into membrane rafts in Jurkat cells, but not in HeLa cells. In contrast, edelfosine inhibited phosphatidylcholine biosynthesis in both HeLa and A549 cells, but not in Jurkat or Peer leukemic cells, before the triggering of apoptosis. These data indicate that edelfosine targets two different subcellular structures in a cell type-dependent manner, namely cell surface lipid rafts in leukemic cells and endoplasmic reticulum in solid tumor cells.
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PMID:Differential targets and subcellular localization of antitumor alkyl-lysophospholipid in leukemic versus solid tumor cells. 1654 Apr 73

The ganglioside patterns have been shown to dramatically change during cell proliferation and differentiation and in certain cell-cycle phases, brain development, and cancer malignancy. To investigate the significance of the ganglioside GM3 in cancer malignancy, we established GM3-reconstituted cells by transfecting the cDNA of GM3 synthase into a GM3-deficient subclone of the 3LL Lewis lung carcinoma cell line (Uemura, S. (2003) Glycobiology, 13, 207-216). The GM3-reconstituted cells were resistant to apoptosis induced by etoposide and doxorubicin. There were no changes in the expression levels of topoisomerase IIalpha or P-glycoprotein, or in the uptake of doxorubicin between the GM3-reconstituted cells and the mock-transfected cells. To understand the mechanism of the etoposide-resistant phenotype acquired in the GM3-reconstituted cells, we investigated their apoptotic signaling. Although no difference was observed in the phosphorylation of p53 at serine-15-residue site by etoposide between the GM3-reconstituted cells and mock-transfected cells, the activation of both caspase-3 and caspase-9 was specifically inhibited in the former. We found that the anti-apoptotic protein B-cell leukemia/lymphoma 2 (Bcl-2) was increased in the GM3-reconstituted cells. Moreover, wild-type 3LL Lewis lung carcinoma cells, which have an abundance of GM3, exhibited no DNA fragmentation following etoposide treatment and expressed higher levels of the Bcl-2 protein compared with the J5 subclone. Thus, these results support the conclusion that endogenously produced GM3 is involved in malignant phenotypes, including anticancer drug resistance through up-regulating the Bcl-2 protein in this lung cancer cell line.
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PMID:Endogenously produced ganglioside GM3 endows etoposide and doxorubicin resistance by up-regulating Bcl-2 expression in 3LL Lewis lung carcinoma cells. 1657 67

Dietary polyphenols, including anthocyanins, are suggested to be involved in the protective effects of fruits and vegetables against cancer. However, anticancer effects of peonidin 3-glucoside have not been clearly demonstrated, with only limited studies being available concerning the inhibitory effect of cyanidin 3-glucoside for tumor cell growth. Therefore, in this study, we have isolated and identified the two bioactive compounds, peonidin 3-glucoside and cyanidin 3-glucoside, from Oryza sativa L. indica, to treat various cancer cells. The results showed that, among analyzed cell lines, HS578T was the most sensitive to peonidin 3-glucoside and cyanidin 3-glucoside. Treatment with peonidin 3-glucoside or cyanidin 3-glucoside resulted in a strong inhibitory effect on cell growth via G2/M arrest. Regarding cell cyclerelated proteins, peonidin 3-glucoside treatment resulted in down-regulation of protein levels of cyclin-dependent kinase (CDK)-1, CDK-2, cyclin B1, and cyclin E, whereas cyanidin 3-glucoside could decrease the protein levels of CDK-1, CDK-2, cyclin B1, and cyclin D1. In addition, cyanidin 3-glucoside or peonidin 3-glucoside also induced caspase-3 activation, chromatin condensation, and cell death. Furthermore, anthocyanins from O. sativa L. indica were evidenced by their inhibition on the growth of Lewis lung carcinoma cells in vivo.
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PMID:Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo. 1657 84


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