Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

MMPT, a thiazolidin compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. However, the related mechanism has yet not been revealed. In this study, we investigated the cellular and molecular events underlying the antitumor function of this compound in human lung adenocarcinoma H1792 cells, focusing on the early cytotoxic effect. Treatment of H1792 cancer cells with MMPT (0.1-100 microM for 24-72 h) resulted in a growth inhibition in a dose and time-dependent manner, determined by MTT assay. This effect was accompanied by apoptosis, evidenced by Nucleosome ELISA, H33258 stained assay, and Sub-G1 analysis. Our data showed that MMPT caused activation of caspase-3, caspase-6 and caspase-8, but not caspase-9. The finding that MMPT induced apoptosis through a membrane-mediated mechanism was supported by the up-regulated expression of Fas (CD95/APO-1), and Fas ligand. Overall, our results demonstrated that MMPT induced growth inhibition of H1792 cells through a Fas-mediated and caspase-dependent apoptosis pathway, which suggested that MMPT might be used as a Fas/FasL and caspases promoter to initiate lung cancer cell apoptosis.
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PMID:MMPT: a thiazolidin compound inhibits the growth of lung cancer H1792 cells via Fas-mediated and caspase-dependent apoptosis pathway. 1941 23

Diallyl disulfide (DADS), an important component of garlic (Allium sativum) derivative, has been demonstrated to exert a potential molecular target against human cancers. We investigated DADS-induced expressions of Apaf1, cystatin B, caspase-3 and FADD (fas-associated protein with death domain) in breast, prostate and lung cancer cells. These showed coincident data when further examined by quantitative reverse transcription-polymerase chain reaction and Western blot analysis. Furthermore, DADS induced a marked amount of Bax translocation, cytochrome c release and activation of caspase-3 and caspase-9. DADS-treated tumor cells triggered mitochondria-mediated signaling pathways that led to a significant increase in apoptosis induction. Further studies with caspase-3 and caspase-9 inhibitors (zDEVD-fmk and zLEHD-fmk, respectively) proved that DADS induces apoptosis through a caspase-3-dependent pathway. DADS is only an agent used in the study. The molecular mechanism presented therefore provides strong additional support to the hypothesis that DADS is a strong inducer of apoptosis through a Bax-triggered mitochondria-mediated and caspase-3-dependent pathway. This study shows clearly that DADS causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. Therefore, the mitochondrial pathway might be the target for cancer chemoprevention and/or chemotherapy by DADS.
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PMID:Diallyl disulfide causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. 1942 21

While lung cancer accounts for approximately 20% of cancer diagnoses, it is the leading cause of tumor-related deaths. The apoptotic effects of 3,5,4'-trihydroxystilbene (resveratrol), dibenzoylmethane (DBM), and their analogues on human lung cancer cells are generally unclear. The aims of this study were to evaluate the apoptotic effects and molecular mechanisms of resveratrol, DBM, and their analogues on human lung cancer cells. The results of the MTT and lactate dehydrogenase (LDH) leakage assays indicated that resveratrol, 3,5,4'-trimethoxy-trans-stilbene (MR-3), and 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB) could inhibit cell population growth and induce cell injury in A549 and CH27 cell lines. Resveratrol and HMDB could induce apoptotic cell death in the A549 and CH27 cell lines. Moreover, cellular growth of the A549 and CH27 cell lines might be inhibited by MR-3 through induction of apoptosis and regulation of the cell cycle. The A549 and CH27 cell lines treated with resveratrol, MR-3, and HMDB showed a time-dependent reduction of mitochondrial membrane potential, and the Bax/Bcl-2 ratio increased gradually with a higher concentration of polyphenols. The resveratrol-, MR-3-, and HMDB-induced apoptosis in the A549 and CH27 cell lines were controlled through activation of caspase-9 and caspase-3 and subsequent cleavage of PARP. In conclusion, we have demonstrated that resveratrol, DBM, and their analogues could be effective candidates for chemoprevention of lung cancer and HMDB might have the strongest ability for inducing apoptosis.
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PMID:Mechanisms of apoptotic effects induced by resveratrol, dibenzoylmethane, and their analogues on human lung carcinoma cells. 1944 15

Aberrant activation of NF-kappaB has been proposed as the major cause of chemoresistance in lung cancer. Low-dose chemotherapeutic agents with limited toxicity and achieving profoundly enhanced efficacy by blocking NF-kappaB activation may be a useful strategy in cancer therapy. Thus, this study was performed to explore the effect of parthenolide, a natural NF-kappaB inhibitor, on human lung cancer A549 cells treated with low-dose oxaliplatin, as well as to determine the potential mechanisms involved. We incubated A549 cells with different concentrations of parthenolide in the absence or presence of a low-dose of oxaliplatin for 48 h. Then, cell proliferation was determined by MTT assay, and flow cytometry was used to study apoptosis. PGE(2) production in culture supernatants was detected by competitive ELISA, while expression of NF-kappaB/p65, COX-2, caspase-3 and caspase-9 proteins were analyzed by Western blot. Finally, compared to parthenolide or oxaliplatin alone, significant improvements in cell apoptosis and growth inhibition indexes were observed in the combined treatment. NF-kappaB/p65, COX-2, and PGE(2) expression were suppressed by the co-application; meanwhile, caspase-3 and caspase-9 proteins were obviously activated. These findings indicate that parthenolide could markedly enhance sensitivity of A549 cells to low-dose oxaliplatin by inhibiting NF-kappaB activation and inducing apoptosis. Parthenolide in combination with a low dose of oxaliplatin may be a beneficial chemotherapeutic strategy for patients who cannot tolerate the severe side effects of the drug at therapeutic concentrations.
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PMID:Sesquiterpene lactone parthenolide markedly enhances sensitivity of human A549 cells to low-dose oxaliplatin via inhibition of NF-kappaB activation and induction of apoptosis. 1977 8

Indole-3-carbinol (I3C) has anti-tumor effects in various cancer cell lines. However, the anti-tumor effect of I3C on human lung cancers has been rarely reported. We investigated the anti-tumor effects and its mechanism of I3C on human lung carcinoma A549 cell line. Treatment of the A549 cells with I3C significantly reduced cell proliferation, increased formations of fragmented DNA and apoptotic body, and induced cell cycle arrest at G0/G1 phase. I3C increased not only the protein levels of cyclin D1, phosphorylated p53, and p21 but also the expression of Fas mRNA. Cleavage of caspase-9, -8, -3 and PARP also was increased by I3C. Treatment with wortmannin significantly suppressed both I3C-induced Ser15 phosphorylation and accumulation of p53 protein. The inhibition of caspase-8 by z-IETD-FMK significantly decreased cleavage of procaspase-8,-3 and PARP in I3C-treated A549 cells. Taken together, these results demonstrate that I3C induces cell cycle arrest at G0/G1 through the activation of p-p53 at Ser 15 and induces caspase-8 mediated apoptosis via the Fas death receptor. This molecular mechanism for apoptotic effect of I3C on A549 lung carcinoma cells may be a first report and suggest that I3C may be a preventive and therapeutic agent against lung cancer.
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PMID:Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells. 2006 30

In the course of our screening for novel modulators on cell cycle progression and apoptosis as anticancer drug candidates, we generated an analogue of sangivamycin, MCS-C2, designated as 4-amino-6-bromo-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. This study was aimed to evaluate the molecular mechanisms on cell cycle arrest and apoptotic induction of MCS-C2 in human lung cancer A549 cells. To investigate the effects of MCS-C2 on cell cycle progression in A549 cells, we measured DNA content of A549 cells treated with 5 microM of HY253 using flow cytometric analysis. The flow cytometric analysis revealed an appreciable G(2) phase arrest in A549 cells treated with 5 micronM of MCS-C2. This MCS-C2-induced G(2) phase arrest is associated with significant up-regulation of p53 and p21(Cip1) in A549 cells. Furthermore, TUNEL assay was used to examine apoptotic induction in A549 cells treated with 5 microM of MCS-C2 for 48 h. In addition, the effects of MCS-C2 on apoptosis-associated proteins in A549 cells were examined using Western blot analysis. The apoptotic induction in MCS-C2-treated A549 cells is associated with cytochrome c release from mitochondria which in turn resulted in the activation of caspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). In conclusion, based on these results, we suggest that MCS-C2 may be a potent cancer chemotherapeutic candidate for use in treating human lung cancer cells via up-regulation and activation of p53.
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PMID:Cell cycle arrest and cytochrome c-mediated apoptotic induction in human lung cancer A549 cells by MCS-C2, an analogue of sangivamycin. 2020 52

Interleukin-24 (IL-24) is a novel tumor suppressor/cytokine gene expressed in normal human melanocytes but for which expression is nearly undetectable in metastatic melanoma. Overexpression of the IL-24 protein has been shown to inhibit tumor cell proliferation and induce apoptosis in many melanoma cell lines, and is now considered a tumor suppressor. Erlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been widely studied for the treatment of human lung cancer and other solid tumors, but the erlotinib-targeted therapy has not been tested in melanoma. The objective of this study is to investigate the potency of erlotinib in suppressing the growth of human melanoma cells and whether IL-24 could enhance the antitumor activity of erlotinib. In cell viability and apoptosis assays, treatment with erlotinib dependently inhibited the growth of different melanoma cell lines and when combined with adenoviral vector-mediated IL-24 gene therapy, a significant increase in cell growth inhibition and apoptosis induction resulted (P<0.05). Immunoblot assay showed that the combination treatment of erlotinib and IL-24 considerably increased the cleavage of caspase-3 and caspase-9 and the expression of Apaf-1 protein in melanoma cells, inducing activation of the Apaf-1-dependent apoptotic pathways. Moreover, this combination treatment markedly inhibited phosphorylation of the EGFR, phosphatidylinositol-3 kinase, and Akt proteins, inactivating the Akt-dependent cell survival signaling pathway. These results show that a combination of IL-24-mediated molecular therapy and EGFR inhibitors such as erlotinib may be a promising treatment strategy for human melanoma and will serve as a basis for guiding the combination treatment designs in future preclinical and clinical trials.
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PMID:IL-24 gene transfer sensitizes melanoma cells to erlotinib through modulation of the Apaf-1 and Akt signaling pathways. 2021 71

Osteopontin (OPN) plays an important role in the development, invasion, and metastasis of malignancies. Recently, several studies have reported that OPN enhances chemoresistance in small-cell lung cancer and breast cancer by blocking caspase-9 and caspase-3-dependent cell apoptosis. The aim of this study was to assess the value of OPN and caspase-3 for predicting tumor recurrence after curative resection in hepatocellular carcinoma (HCC) patients. We found that OPN expression increased concordantly with increasing metastatic potential in human HCC cell lines, whereas caspase-3 expression declined. In a tumor tissue microarray immunohistochemical analysis, we found that patients with higher levels of OPN and lower levels of caspase-3 had a significantly poorer prognosis than patients with lower OPN and higher caspase-3 levels. The combination of OPN and caspase-3 expression thus served as an effective prognosticator. These findings suggest that OPN alone or in combination with caspase-3 may act as an independent indicator for HCC patients after curative resection.
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PMID:Expression and prognostic significance of osteopontin and caspase-3 in hepatocellular carcinoma patients after curative resection. 2034 80

Artemisia annua is a rich source of many bioactive substances, and in our recent work, a new sesquiterpene, (Z)-7-acetoxy-methyl-11-methyl-3-methylene-dodeca-1,6,10-triene (AMDT), was isolated and identified from hairy roots culture of A. annua, and its bioactivity was characterized in this work. AMDT showed moderate cytotoxic activities against the human tumor cell lines of HO8910 (ovary), 95-D (lung), QGY (liver) and HeLa (cervix) by MTT assay, whose IC(50) values were ranged within 52.44-73.3 microM. As lung cancer is the No. 1 killer of global cancer patients, our interest is to investigate the ability of AMDT in inducing apoptosis of 95-D tumor cells. The 95-D cell growth was inhibited by AMDT, and the flow cytometry analysis showed its cell cycle was arrested in the G1 phase. The apoptotic rate of the cells increased in a dose-dependent manner. AMDT lowered the mitochondrial membrane potential and increased the expression of caspase-9 and -3. These results revealed that AMDT could efficiently induce 95-D cell apoptosis through mitochondrial dependent pathway, and it may be a potential chemotherapeutic agent.
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PMID:Inhibition of tumor cell proliferation and induction of apoptosis in human lung carcinoma 95-D cells by a new sesquiterpene from hairy root cultures of Artemisia annua. 2036 22

The molecular mechanism and possible signaling pathway of apigenin-induced cytotoxicity and apoptosis in human lung cancer cells has not been reported. We investigated the role of ROS, Ca2+, caspases and Bax proteins and mitochondria membrane potential in apigenin-induced apoptosis in A549 cells. Cells were incubated with different concentrations of apigenin then cell morphological changes, DNA damage, cell viability and apoptosis were determined by Comet assay, and flow cytometric analysis. Sub-G1 phase was also examined. Western blot analysis was used to determined the levels of Bax and Bcl-2 and apoptosis associated proteins, and confocal laser microscope for examining the translocation of associated protein after exposed to apigenin. The results indicated that apigenin induced morphological changes, decreased percentage of viable cells and induced apoptosis dose- and time-dependently. DAPI staining and Comet assay also confirmed that apigenin-induced DNA condensation and damage. The levels of caspase-3, -8 and -9 involved in apigenin-induced apoptosis indicating caspase-dependent pathway was induced by apigenin. Western blotting showed that apigenin promoted cytochrome c levels and also induced dysfunction of mitochondria leading to the release of cytochrome c, AIF and Endo G, causing the activation of caspase-9 and -3, then apoptosis in A549 cells.
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PMID:Apigenin induces caspase-dependent apoptosis in human lung cancer A549 cells through Bax- and Bcl-2-triggered mitochondrial pathway. 2042 72


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