Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.
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PMID:Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death. 1586 11

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

A novel small molecule, 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (EOD), was synthesized in our laboratory. Previously, we reported pharmacological properties of EOD, triggering apoptosis in Human umbilical vein endothelial cells (HUVECs). Here, we further investigated the effects of EOD on the growth of A549 human lung cancer cells. EOD treatment induced apoptosis in A549 cells via up-regulating the expression of P53 protein, blocking cell cycle partly at G1 phase, and ultimately activating caspase-3. In contrast, caspase-8 might be irrelevant to EOD-triggered apoptosis. This study indicated that EOD might be a potential chemopreventive agent for lung cancer. The work would encourage us to add more novel compounds to our 'library' of small molecules derived through modern synthetic organic chemistry, and would drive us to determine the proteins that the compounds target.
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PMID:Discovery of a novel small molecule, 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol, that induces apoptosis in A549 human lung cancer cells. 1588 4

Smoking is a major cause of human lung cancer. Past studies suggest that apoptosis might influence the malignant phenotype, but little is known about the association between apoptosis and cigarette smoke (CS)-induced lung pathogenesis. Using an in situ cell death detection kit (TA300), the association of CS with apoptosis was determined in a concentration-dependent manner. Furthermore, the expression of related proteins were investigated in the terminal bronchiole areas of the lung tissue from rats exposed to CS. Results showed that the expression of phosphotyrosine proteins was increased significantly in lung tissue of rats exposed to CS from 5 to 15 cigarettes. Using Western blotting and immunoprecipitation assay, Fas, a death receptor, was proved just be one of these phosphotyrosine proteins. CS triggered activation of MAP kinase (p38/JNK or ERK2) pathway, which led to Jun or p53 phosphorylation and FasL induction links Fas phosphorylation. Further, smoke treatment produced an increase in the level of proapoptotic proteins (Bax, t-Bid, cytochrome c and caspase-3), but a decline in Bcl-2, procaspase-8 and procaspase-9 proteins. Thus, CS-induced apoptosis may result from two main mechanisms, one is the activation of p38/JNK-Jun-FasL signaling, and the other is stimulated by the stabilization of p53, increase in the ratio of Bax/Bcl-2, release of cytochrome c; thus, leading to activation of caspase cascade.
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PMID:Induction of apoptosis in the lung tissue from rats exposed to cigarette smoke involves p38/JNK MAPK pathway. 1597 Feb 77

The possible antiproliferative and apoptotic inducing potentials of fresh juice prepared from Scutellaria barbata (SBJ) and warmed water extract of Radix Sophorae Tonkinensis (RSTE) have been tested on a series of cancer cell lines, including HepG2 hepatoblastoma, Hep3B hepatocellular carcinoma, MDA-MB231 breast carcinoma, A549 lung cancer and KG-1 acute myelogenous leukaemia in vitro. Both SBJ and RSTE were able to inhibit the growth of cancer cell lines and induce apoptosis. Further analysis of the action of RSTE on HepG2 cells suggested that the activity of the central machinery of apoptosis, caspase 3, was significantly elevated. Oligo-nucleosomal length DNA fragments formation was readily detected by TdT-mediated dUTP nick end labelling assay after RSTE treatment. Taken together, we believe that, although Radix Sophorae Tonkinensis was demonstrated to have toxic components including matrine and oxymatrine, it is still worthwhile to further investigate its anti-cancer potential under a safety toxicological precaution.
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PMID:Activities of fresh juice of Scutellaria barbata and warmed water extract of Radix Sophorae Tonkinensis on anti-proliferation and apoptosis of human cancer cell lines. 1601 72

Lung cancer, the leading cause of cancer-related deaths in both men and women, is the consequence of disordered apoptosis, induction of which may have therapeutic utility. Hyperthermia has been identified as a stimulus for apoptosis. We investigated the mechanism of hyperthermia-induced cell death in ras-transformed lung cells. Effect of hyperthermia (43 degrees C for 180 min) was compared between two cell lines, an immortalized (sv-40) normal human bronchial epithelial (BEAS2-B) and its malignant transformed (H-ras transfected) counterpart (BZR-T33). Survival after hyperthermia: 7-d growth culture BEAS2-B, 1.03 +/- 0.007 and BZR-T33, 0.39 +/- 0.008 (P < 0.05); clonogenic assays BEAS2-B, 0.76 +/- 0.003 and BZR-T33, 0.41 +/- 0.004 (P < 0.05). Hoechst positive (apoptotic) cells: BEAS2-B, 11 +/- 3% and BZR-T33, 78 +/- 5% (P < 0.05). TUNEL, DNA fragmentation, and Annexin-V all corroborate this result. Western blot comparing the effect of hyperthermia in BZR-T33 cells to BEAS2-B cells revealed: TRAIL and FAS-L displayed significant increases (threefold and twofold, respectively); caspase-3 showed a decrease in uncleaved form and an increase in cleaved form, and a 50-fold increase in activity effectively blocked with the caspase-3 inhibitor DEVD-fmk; caspase-9 showed near depletion of uncleaved; poly (ADP-ribose) polymerase (PARP) degradation was clearly visible during heating. After hyperthermia, gene expression demonstrates a 5.7-fold increase in TRAIL and insignificant changes in tumor necrosis factor-alpha (TNF-alpha), FAS-L, and caspases 3, 8, 9 in transformed cells. Data demonstrated that hyperthermia induces apoptosis in transformed cells, and that apoptosis is mediated by caspase-3 as a result of activation of cell-death membrane receptors of the tumor-necrosis-factor family. In summary, these data suggest that hyperthermia could become an additional modality in the multidisciplinary approach to the treatment of lung cancer.
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PMID:A mechanism of hyperthermia-induced apoptosis in ras-transformed lung cells. 1611 53

Hyperthermia increases cytotoxicity of various antineoplastic agents. We investigated the cytotoxic effects of Gemcitabine and/or hyperthermia on BZR-T33 (human non-small-cell lung cancer cells) in vitro and in immune-suppressed athymic nude mice. Isobologram analysis of monolayer cell cultures for cytotoxicity demonstrates a synergistic interaction between hyperthermia and Gemcitabine. Clonogenic results show significant reductions in surviving fractions and colony size for both therapies; greatest reduction was for the combined therapy group. Using cell cycle analysis, hyperthermia enhanced Gemcitabine-induced G2-M arrest resulting in destruction of 3.5 log cells. Apoptotic studies (Annexin-V FITC staining) showed that hyperthermia augmented Gemcitabine-induced apoptosis. Transmission electron microscopy demonstrated pathology observed in cultures exposed to either therapy present in cultures exposed to both therapies. Studies in nude mice show that the combination therapy group had both an initial decrease in tumor size, and a significantly delayed rate of growth. Additionally, using tumor material harvested from nude mice two days after end to treatment reveals a significantly greater apoptotic index and significantly smaller mitotic index for the combined therapy group. Western blots of the same tumor material, showed that heat shock protein 70 was not significantly increased, however, caspase-3 activity of was significantly increased because of the combined therapy. In conclusion, the combined therapy is synergistic in effect because of hyperthermia enhancing Gemcitabine-induced apoptosis.
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PMID:Synergistic interaction of hyperthermia and Gemcitabine in lung cancer. 1613 7

The fragile histidine triad (FHIT) gene is a frequent target of deletions in lung cancer. Previous studies have shown that FHIT gene transfer into lung cancer cells lacking FHIT expression results in induction of apoptosis. However, the effect of FHIT expression on apoptosis induced by chemotherapeutic agents and its intracellular mechanism is poorly understood. This study was undertaken to elucidate the effect of FHIT expression and the role of Bcl-2-caspase signaling in paclitaxel-induced apoptosis in lung cancer cells. NCI-H358 lung cancer cells, which lack FHIT expression, were stably transfected with plasmid vector containing FLAG-tagged wildtype FHIT. We investigated effects of paclitaxel on apoptosis, activation of caspase system and expression of Bcl-2 family. We next evaluated whether these effects were reversed by blocking FHIT expression using siRNA. Paclitaxel enhanced apoptosis in FHIT-expressing cells compared to that in control vector-transfected cells, and this enhancement was suppressed by siRNA treatment. Activities of caspase-3 and caspase-7, but not of caspase-8, were higher in FHIT-expressing cells than in control vector-transfected cells, and this was reduced by siRNA treatment. When caspase activation was blocked by a pan-caspase inhibitor in FHIT-expressing cells, paclitaxel-induced apoptotic cell death was decreased similar to that in control vector-transfected cells. Bcl-2 and Bcl-xL expressions were down-regulated after paclitaxel treatment in FHIT-expressing cells, whereas Bax and Bad expressions were up-regulated. These were reversed by siRNA treatment. These results indicate that paclitaxel-induced apoptosis enhanced by FHIT expression in lung cancer cells might be associated with modulation of Bcl-2-caspase signaling.
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PMID:FHIT protein enhances paclitaxel-induced apoptosis in lung cancer cells. 1623 22

Previously we found that 3,4-(methylenedioxy)-1-(2',3'-epoxypropyl)-benzene (safrole oxide) induced a typical apoptosis in A549 human lung cancer cells. In this study, we further investigated which caspases were activated by safrole oxide during the apoptosis. The data showed that the activity of caspase-3, -8, and -9 was significantly enhanced by the compound, which suggested that safrole oxide might be used as a caspase promoter to initiate lung cancer cell apoptosis.
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PMID:Safrole oxide induces apoptosis by activating caspase-3, -8, and -9 in A549 human lung cancer cells. 1624 24

Aflatoxin B1 (AFB1) is a potent dietary hepatocarcinogen in animals and probably in humans. Mutations (and altered expression) of the tumor suppresser gene p53 have been observed in liver tumors from patients exposed to high dietary AFB1. Inhalation of AFB1-laden grain dusts has been associated with an increased incidence of lung cancer in humans as well. We examined the effects of low concentrations of AFB1 on the expression of p53 and MDM2 in human bronchial epithelial cells (BEAS-2B) transfected with cDNA for either cytochrome P450 (CYP) 1A2 (B-CMV1A2) or CYP 3A4 (B3A4), two isozymes that are responsible for AFB1 activation in human liver and possibly the lung. Untreated B-CMV1A2 and B3A4 cells constitutively expressed p53. Exposure to a range (0.015-15 microM for 30 min) of AFB1 concentrations caused a concentration-dependent decline in p53 expression in B-CMV1A2 cells, and to a lesser extent, in B3A4 cells. The AFB1-mediated decrease in p53 continued for at least 12 h after 30-min exposures to 1.5 muM AFB(1). Mirroring the decrease in p53 expression was a concentration-dependent increase in the expression of the 76-kDa MDM2 isoform in B-CMV1A2 and B-3A4 cells. Interestingly, AFB1 did not induce DNA laddering, an indicator of apoptotic cell death, but proteolytic activation of caspase-3 was detected in AFB1-treated B-CVM1A2 cells. In total, these data show that low, environmentally-relevant concentrations of AFB1 alter the expression of p53 and MDM2 in these human lung cells, and that cells that stably express CYP 1A2 were more susceptible to this effect than nontransfected, or 3A4-expressing cells.
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PMID:Aflatoxin B1 alters the expression of p53 in cytochrome P450-expressing human lung cells. 1628 Mar 84


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