Overexpression of Smac Promotes Cisplatin-Induced Apoptosis by Activating Caspase-3 and Caspase-9 in Lung Cancer A549 Cells

2013 ◽  
Vol 28 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Sida Qin ◽  
Chengcheng Yang ◽  
Xifang Wang ◽  
Chongwen Xu ◽  
Shuo Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
A549 Cells ◽  
Caspase 9 ◽  
Induced Apoptosis

Synthesis of 5-Alkynyltetrandrine Derivatives and Evaluation of their Anticancer Activity on A549 Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1454-1462 ◽  
Author(s):  
Nana Niu ◽  
Tingli Qu ◽  
Jinfang Xu ◽  
Xiaolin Lu ◽  
Graham J. Bodwell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Coupling Reactions ◽  
Apoptotic Pathway ◽  
Future Design ◽  
Cyt C ◽  
Induced Apoptosis

Background: Lung cancer is one of the most prevalent malignancies and thus the development of novel therapeutic agents for managing lung cancer is imperative. Tetrandrine, a bis-benzyltetrahydroisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, has been found to exert cytotoxic effects on cancerous cells. Methods: A series of 5-alkynyltetrandrine derivatives was synthesized via the Sonogashira cross-coupling reactions and evaluated as potential anti-tumor agents. The anti-tumor activities of 12 compounds on lung cancer cells (A549) were evaluated using the MTT method. The population of apoptotic cells was measured using a TUNEL assay. Real-time PCR quantified the gene expression levels of Bcl-2, Bax, survivin and caspase-3. The content of Cyt-C was detected using a Human Cyt-C ELISA kit. Results: Most of these compounds exhibited better activities than tetrandrine itself on A549 cells. Among them, compound 7 showed the highest cytotoxicity among the tested compounds against human lung adenocarcinoma A549 cells with an IC50 of 2.94 µM. Preliminary mechanistic studies indicated that compound 7 induced apoptosis of human lung cancer A549 cells and increased the level of the proapoptotic gene Bax, release of Cyt-C from mitochondria and activation of caspase-3 genes. Conclusion: The results suggest that compound 7 exerts its antitumor activity against A549 cells through the induction of the intrinsic (mitochondrial) apoptotic pathway. These findings will contribute to the future design of more effective anti-tumor agents in lung cancer therapy.

scholarly journals Resistin increases cisplatin-induced cytotoxicity in lung adenocarcinoma A549 cells via a mitochondria-mediated pathway

2021 ◽  
Author(s):  
Wei-Jing Gong ◽  
Tao Zhou ◽  
Jia-Qiang Xu ◽  
Yi-Fei Huang ◽  
Li-Ping Xiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Reactive Oxygen Species Generation ◽  
A549 Cells ◽  
Chemotherapeutic Agents ◽  
Lung Cancer Patients ◽  
M Phase ◽  
Advanced Stages ◽  
Lung Adenocarcinoma A549 ◽  
Induced Apoptosis

Abstract Lung cancer is the most commonly diagnosed cancer with a high mortality rate. Cisplatin is one of the most important chemotherapeutic agents for the treatment of lung cancer patients, especially in advanced stages. Recent studies showed that cisplatin may interact with mitochondria which may partly account for its cytotoxicity. In the study, we explored the effect of resistin on cisplatin-induced cytotoxicity in A549 cells and assessed whether mitochondria-dependent apoptosis was involved. Our results found that 25 ng/ml resistin could significantly increase cisplatin-induced apoptosis and G2/M phase arrest, enhance reactive oxygen species generation, exacerbate the collapse of mitochondrial membrane potential, promote the distribution of cytochrome C in the cytoplasm from mitochondria, and activate caspase 3. Therefore, the results suggested that resistin might increase cisplatin-induced cytotoxicity via a mitochondria-mediated pathway in A549 cells. However, the precise mechanism has yet to be explored in the future.

scholarly journals Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Xiang-Bo Jia ◽  
Quan Zhang ◽  
Lei Xu ◽  
Wen-Jian Yao ◽  
Li Wei
Keyword(s):  
Lung Cancer ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Human Lung ◽  
Mapk Pathway ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Caspase 9 ◽  
Lotus Leaf

Abstract Background Leaves of the natural plant lotus are used in traditional Chinese medicine and tea production. They are rich in flavonoids. Methods In this study, lotus leaf flavonoids (LLF) were applied to human lung cancer A549 cells and human small cell lung cancer cells H446 in vitro to verify the effect of LLF on apoptosis in these cells through the ROS/p38 MAPK pathway. Results LLF had no toxic effect on normal cells at concentrations up to 500 µg/mL, but could significantly inhibit the proliferation of A549 cells and H446 cells. Flow cytometry showed that LLF could induce growth in A549 cells. We also found that LLF could increase ROS and MDA levels, and decrease SOD activity in A549 cells. Furthermore, qRT-PCR and western blot analyses showed that LLF could upregulate the expression of p38 MAPK (p-p38 MAPK), caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9 and Bax and downregulate the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1, and Bcl-2 in A549 cells. Results of HPLC showed that LLF mainly contain five active substances: kaempferitrin, hyperoside, astragalin, phloridzin, and quercetin. The apoptosis-inducing effect of LLF on A549 cells came from these naturally active compounds. Conclusions We have shown in this study that LLF is a bioactive substance that can induce apoptosis in A549 cells in vitro, and merits further research and development.

scholarly journals The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Hosami ◽  
Azadeh Manayi ◽  
Vahid Salimi ◽  
Farshad Khodakhah ◽  
Mitra Nourbakhsh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Caspase 3 ◽  
Cannabis Sativa ◽  
A549 Cells ◽  
Echinacea Purpurea ◽  
G1 Phase ◽  
Cell Cycle Distribution ◽  
Cb2 Receptor ◽  
Anti Cancer

Abstract Background Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects of Echinacea purpurea (as a non-cannabinoid plant) and Cannabis sativa (as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study. Methods The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7′-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit. Results Echinacea purpurea (EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations of Cannabis sativa (CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells. Conclusions The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents. Graphical abstract

Radix Tetrastigma Inhibits the Non-Small Cell Lung Cancer via Bax/Bcl-2/Caspase-9/Caspase-3 Pathway

2021 ◽  
pp. 1-13
Author(s):  
Yonglu Li ◽  
Yaxuan Wang ◽  
Xin Yu ◽  
Ting Yu ◽  
Xiaodong Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Caspase 9

Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

2001 ◽  
Vol 280 (1) ◽  
pp. L10-L17 ◽  
Author(s):  
Han-Ming Shen ◽  
Zhuo Zhang ◽  
Qi-Feng Zhang ◽  
Choon-Nam Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Alveolar Macrophages ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

scholarly journals Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro

2018 ◽  
Vol 48 (4) ◽  
pp. 1433-1442 ◽  
Author(s):  
Jie Min ◽  
Hua Shen ◽  
Wang Xi ◽  
Qing Wang ◽  
Liang Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Caffeic Acid ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Caspase 9 ◽  
Anti Cancer

Background/Aims: Caffeic acid (CA) is known to possess multiple biological activities including anti-cancer activities. However, the molecular mechanisms underlying these activities in non-small-cell lung cancer (NSCLC) cells are not fully understood. We attempted to clarify whether CA could enhance paclitaxel (PTX)-induced cytotoxicity in H1299 cells. Methods: First, we tested the cytotoxic effects in both H1299 cells and normal human Bease-2b cells by cell proliferation experiments. Next, we use Annexin V/propidium iodide apoptosis analysis and flow cytometric analysis to investigate apoptosis and cell cycle arrest under the treatments mentioned above. To further pinpoint changes in apoptosis, we tested the caspase-associated apoptotic pathway, which involves the activities of caspase-3 and caspase-9. Moreover, apoptosis-related proteins and MAPK pathway proteins were examined by western blot. An H1299 xenograft nude mice model was used to further evaluate the tumor-suppressing effects of CA and PTX in vivo. Results: Combination treatment with low-dose CA and PTX decreased the proliferation of NSCLC H1299 cells but not normal Beas-2b cells. Flow cytometry showed that H1299 cells were arrested in the sub-G1 phase and apoptosis was significantly increased in H1299 cells after CA treatment. Caspase-3 and caspase-9 activities were both increased after CA treatment. Furthermore, CA increased the PTX-induced activation of Bax, Bid, and downstream cleaved PARP, and phosphorylation of extracellular signal regulated kinase1/2 and c-Jun NH2-terminal protein kinase1/2. An in vivo tumor-suppression assay demonstrated that CA and PTX combined treatment exerted a more effective suppressive effect on tumor growth in H1299 xenografts without causing significant adverse effects. Conclusions: Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.

Parathyroid hormone-related protein ameliorates death receptor-mediated apoptosis in lung cancer cells

2003 ◽  
Vol 285 (6) ◽  
pp. C1429-C1436 ◽  
Author(s):  
Randolph H. Hastings ◽  
Flavio Araiza ◽  
Douglas W. Burton ◽  
Lu Zhang ◽  
Maxwell Bedley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Cancer Progression ◽  
Caspase 3 ◽  
Death Receptor ◽  
Related Protein ◽  
Caspase 9 ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone-related protein (PTHrP) is expressed in more advanced, aggressive tumors and may play an active role in cancer progression. This study investigated the effects of PTHrP on apoptosis after UV irradiation, Fas ligation, or staurosporine treatment in BEN human squamous lung carcinoma cells. Cells at 70% confluency were treated for 24 h with 100 nM PTHrP-(1-34), PTHrP-(38-64), PTHrP-(67-86), PTHrP-(107-139), or PTHrP-(140-173) in media with serum, exposed for 30 min to UV-B radiation (0.9 mJ/cm2), and maintained for another 24 h. Caspase-3, caspase-8, and caspase-9 activities increased fivefold. Pretreatment with PTHrP-(1-34) and PTHrP-(140-173) ameliorated apoptosis after UV irradiation, as indicated by reduced caspase activities, increased cell protein, decreased nuclear condensation, and increased clonal survival. Other peptides had no effect on measures of apoptosis. PTHrP-(140-173) also reduced caspase activities after Fas ligation by activating antibody, but neither peptide had effects on caspase-3 or caspase-9 activity after 1 μM staurosporine. These data indicate that PTHrP-(1-34) and PTHrP-(140-173) protect against death receptor-induced apoptosis in BEN lung cancer cells but are ineffective against mitochondrial pathways. PTHrP contributes to lung cancer cell survival in culture and could promote cancer progression in vivo. The mechanism for the protective effect against apoptosis remains to be determined.

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