scholarly journals 125 I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, Survivin，Livin and Caspase-9 expression in lung carcinoma xenografts

2020 ◽  
Author(s):  
Qing Jin ◽  
Cunzhi Lin ◽  
Xinhong Zhu ◽  
Yiwei Cao ◽  
Caihong Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Caspase 3 ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Caspase 8 ◽  
125I Seed ◽  
Caspase 9 ◽  
Ki 67 ◽  
Seed Irradiation

Abstract Background: Lung cancer is a fatal disease and a serious health problem worldwide. Patients are usually diagnosed at an advanced stage, and the effectiveness of chemotherapy for such patients is very limited. Iodine 125 seed(125I) irradiation can be used as an important adjuvant treatment for lung carcinoma. The purpose of this study was to examine the role of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on apoptosis. Methods: 40 mice with A549 lung adenocarcinoma xenografts were randomly divided into 4 groups: control group (n=10), sham seed (0 mCi) implant group (n=10), 125I seed (0.6 mCi) implant group (n=10) and 125I seed (0.8 mCi) implant group (n=10), respectively. The body weight and tumor volume, were recorded every four days until the end of the study. Apoptotic cells were checked by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and activities of caspase-3 and caspase-8 enzyme were tested. Expression of P21, survivin, livin, caspase-9 and proliferating cell nuclear antigen (Ki-67) was detected with immunohistochemical staining. Results: The results of TUNEL staining assays showed that 125I seed irradiation suppresses the growth of lung cancer xenografts in nude mice and induced apoptosis. The activity of caspase-3 and caspase-8 was significantly higher. The expression levels Ki67, survivin and livin were substantially downregulated, while P21 and caspase-9 protein expression were significantly increased following 125I seed irradiation. This study revealed that 125I seed irradiation could significantly change apoptosis-related protein in human lung cancer xenografts. Conclusions: Overall, our study demonstrates that radiation exposure by 125I seedscould be a new treatment option for lung cancer.

scholarly journals 125I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Qing Jin ◽  
Cunzhi Lin ◽  
Xinhong Zhu ◽  
Yiwei Cao ◽  
Caihong Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Caspase 8 ◽  
125I Seed ◽  
Caspase 9 ◽  
Ki 67 ◽  
125I Seeds ◽  
Seed Irradiation

Abstract Background Lung cancer is a fatal disease and a serious health problem worldwide. Patients are usually diagnosed at an advanced stage, and the effectiveness of chemotherapy for such patients is very limited. Iodine 125 seed (125I) irradiation can be used as an important adjuvant treatment for lung carcinoma. The purpose of this study was to examine the role of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on apoptosis. Methods 40 mice with A549 lung adenocarcinoma xenografts were randomly divided into 4 groups: control group (n = 10), sham seed (0 mCi) implant group (n = 10), 125I seed (0.6 mCi) implant group (n = 10) and 125I seed (0.8 mCi) implant group (n = 10), respectively. The body weight and tumor volume, were recorded every 4 days until the end of the study. Apoptotic cells were checked by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and activities of caspase-3 and caspase-8 enzyme were tested. Expression of P21, survivin, livin, caspase-9 and proliferating cell nuclear antigen (Ki-67) was detected with immunohistochemical staining. Results The results of TUNEL staining assays showed that 125I seed irradiation suppresses the growth of lung cancer xenografts in nude mice and induced apoptosis. The activity of caspase-3 and caspase-8 was significantly higher. The expression levels Ki67, survivin and livin were substantially downregulated, while P21 and caspase-9 protein expression were significantly increased following 125I seed irradiation. This study revealed that 125I seed irradiation could significantly change apoptosis-related protein in human lung cancer xenografts. Conclusions Overall, our study demonstrates that radiation exposure by 125I seeds could be a new treatment option for lung cancer.

scholarly journals 125 I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, Survivin，Livin and Caspase-9 expression in lung carcinoma xenografts

2020 ◽  
Author(s):  
Lijun Wang ◽  
Cunzhi Lin ◽  
Qing Jin ◽  
Xinhong Zhu ◽  
Yiwei Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Caspase 8 ◽  
125I Seed ◽  
Caspase 9 ◽  
Ki 67 ◽  
125I Seeds ◽  
Seed Irradiation

Abstract Background: Lung cancer is a fatal disease and a serious health problem worldwide. Patients are usually diagnosed at an advanced stage, with the effectiveness of chemotherapy for such patients being very limited. Iodine 125 seed(125I) irradiation can be used as an important adjuvant treatment for lung carcinoma. The purpose of this study was to examine the effects of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on apoptosis. Methods: A group of 40 mice bearing A549 lung adenocarcinoma xenografts were randomly divided into 4 groups: control group (n=10), sham seed (0 mCi) implant group (n=10), 125I seed (0.6 mCi) implant group (n=10) and 125I seed (0.8 mCi) implant group (n=10), respectively. The body weight and tumor volume, was recorded every four days until the end of the study. Apoptotic cells were checked with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and activities of caspase-3 and caspase-8 enzyme were tested. Expression of P21, survivin, livin, caspase-9 and proliferating cell nuclear antigen (Ki-67) was detected with immunohistochemical staining. Results: The results of TUNEL staining assays shows that 125I seed irradiation suppresses the growth of lung cancer xenografts in nude mice and induces apoptosis. The activity of caspase-3 and caspase-8 was significantly higher. The expression levels Ki67, survivin and livin were substantially downregulated, while P21 and caspase-9 protein expression was significantly increased following 125I seed irradiation. This study revealed that 125I seed irradiation could significantly change apoptosis-related protein in human lung cancer xenograft. Conclusions: Overall, our study demonstrates that radiation exposure by 125I seeds has been expected as a new treatment option for lung cancer.

Mechanism of inhibitory effect of terpenoid compound from Achillea millefolium on human lung cancer cell proliferation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15058-e15058
Author(s):  
Siming Wang ◽  
Yu Wang ◽  
Yibing Wu ◽  
Mei Dong ◽  
Zhiyu Ni
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Human Lung ◽  
P53 Protein ◽  
Human Lung Cancer ◽  
Achillea Millefolium ◽  
Caspase 8 ◽  
Lung Cancer Cell

e15058 Background: A large number of reports have found that many components in traditional Chinese medicine preparations have obvious anti-tumor activities, and most of these effective components are realized by inducing tumor cell apoptosis. In this part of the experiment, we studied terpenoid compound (3β-acetoxy-1β,4α-dihydroxy-11αH-eudesman-12,6α-olide Achillea millefolium A) from Achillea millefolium anti-cancer mechanism, to determine whether this compound by inducing cell apoptosis plays its antitumor activity of cell proliferation. Methods: (1) The apoptosis of NCI-H292 cells treated with 1 μmol/L and 10 μmol/L Achillea millefolium A was detected by Annexinov-FITC /PI stain. (2) The apoptosis of NCI-H292 cells treated with 10 μmol/L Achillea millefolium A for 12 h and 24 h was detected by in situ end labeling. (3) The changes of p53, Bax, Caspase-3/8/12 and GRP78 in NCI-H292 cells were detected by Western blotting. Results: (1) Effects of Achillea millefolium A on apoptosis of NCI-H292 cells: The apoptosis rate of NCI-H292 cells treated with 1 μmol/L and 10 μmol/ L Achillea millefolium A for 12 h was (15.31)% and (17.84)% respectively. The apoptosis rate of NCI-H292 cells treated with 1 μmol/L and 10 μmol/ L Achillea millefolium A for 12 h was (15.37)% . (2), TUNEL method further verified the cell apoptosis: NCI-H292 cells were treated with 10 μmol/L Achillea millefolium A for 12 h and 24 h, and the positive cells accounted for (13.89)% and (28.37)% respectively, compared with blank control group (4.17)%. (3), Achillea millefolium A up-regulated the expression of p53 protein, Bax protein, Caspase-3/8/12 and GRP78 protein in NCI-H292 cells: After NCI-H292 cells were treated with 1 μmol/L and 10 μmol/ L Achillea millefolium A for 24 h, the expressions of p53, Bax, Caspase-3 and Caspase-8 in NCI-H292 cells were significantly up-regulated. After treatment with 1 μmol/L and 10 μmol/ L Achillea millefolium A for 12 h, the expression of Caspase-12 and GRP78 increased significantly. Conclusions: Achillea millefolium A is a terpenoid compound with obvious apoptosis-inducing activity on human lung cancer cell line NCI-H292. Achillea millefolium A induced apoptosis of NCI-H292 cells was the result of multiple pathways. Achillea millefolium A can up-regulate p53 protein, and then up-regulate Bax, and then activate Caspase-3 protein expression. At the same time, the expression of caspase-3 protein was further increased by activating caspase-8, and apoptosis was induced by both exogenous and endogenous pathways. Notably, the complex of ER stress pathway GRP78 and caspase-12 may also be one of the mechanisms by which Achillea millefolium A induces apoptosis in NCI-H292 cells.

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.

Effects of 5,6-Dihydroxy-2,4-Dimethoxy-9,10-Dihydrophenanthrene on G2/M Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

2016 ◽  
Vol 44 (07) ◽  
pp. 1473-1490 ◽  
Author(s):  
Wipada Duangprompo ◽  
Kalaya Aree ◽  
Arunporn Itharat ◽  
Pintusorn Hansakul
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Caspase 3 ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Apoptotic Cells ◽  
Mrna Levels ◽  
Cycle Arrest

5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (HMP) is an active compound isolated from the rhizome extracts of Dioscorea membranacea Pierre, a Thai medicinal plant. This study aimed to investigate the growth-inhibitory and apoptosis-inducing effects of HMP in human lung cancer A549 cells. The antiproliferative and cytotoxic effects of HMP were analyzed by a Sulforhodamine B assay. Cell division, cell cycle distribution and membrane asymmetry changes were each performed with different fluorescent dyes and then analyzed by flow cytometry. Real-time PCR and immunoblotting were used to detect cell cycle- and apoptosis-related mRNA levels and proteins, respectively. The nuclear morphology of the cells stained with DAPI and DNA fragmentation were detected by fluorescence microscopy and gel electrophoresis, respectively. The results showed that HMP exerted strong antiproliferative and cytotoxic activities in A549 cells with the highest selectivity index. It halted the cell cycle in [Formula: see text]/M phase via down-regulation of the expression levels of regulatory proteins Cdc25C, Cdk1 and cyclinB1. In addition, HMP induced early apoptotic cells with externalized phosphatidylserine and subsequent apoptotic cells in sub-[Formula: see text] phase. HMP increased caspase-3 activity and levels of the cleaved (active) form of caspase-3 whose actions were supported by the cleavage of its target PARP, nuclear condensation and DNA apoptotic ladder. Moreover, HMP significantly increased the mRNA and protein levels of proapoptotic Bax as well as promoted subsequent caspase-9 activation and BID cleavage, indicating HMP-induced apoptosis via both intrinsic and extrinsic pathways. These data support, for the first time, the potential role of HMP as a cell-cycle arrest and apoptosis-inducing agent for lung cancer treatment.

Calmodulin inhibition contributes to sensitize TRAIL-induced apoptosis in human lung cancer H1299 cells

2009 ◽  
Vol 87 (6) ◽  
pp. 919-926 ◽  
Author(s):  
Mi-kyung Hwang ◽  
Yong Ki Min ◽  
Seong Hwan Kim
Keyword(s):  
Lung Cancer ◽  
Enzyme Inhibitors ◽  
Human Lung ◽  
Therapeutic Potential ◽  
Human Lung Cancer ◽  
Caspase 8 ◽  
Death Domain ◽  
Akt Phosphorylation ◽  
Apoptosis Protein ◽  
Induced Apoptosis

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells. However, TRAIL alone is not effective in treating TRAIL-resistant tumors. We evaluated the effect of 180 enzyme inhibitors on TRAIL-induced apoptosis in human lung cancer H1299 cells, and found fluphenazine-N-2-chloroethane (a calmodulin (CaM) antagonist) sensitized TRAIL-induced apoptosis. Interestingly, in the presence of TRAIL, it increased caspase-8 binding to the Fas-associated death domain (FADD), but decreased binding of FADD-like interleukin-1β-converting enzyme inhibitory proteins (FLIPs). Additionally, its combination with TRAIL inhibited Akt phosphorylation. These results were consistently observed in cells treated with CaM siRNA. We suggested the blockade of CaM could sensitize lung cancer cells to TRAIL-induced apoptosis in at least 2 ways: (i) it can activate death-inducing signaling complex mediated apoptosis by inhibiting TRAIL-induced binding of FLIP and TRAIL-enhanced binding of caspase-8 to FADD; (ii) it can inhibit Akt phosphorylation, consequently leading to decreased expression of anti-apoptotic molecules such as FLIP and members of the inhibitor of apoptosis protein family. This study suggests the combination of CaM antagonists with TRAIL may have the therapeutic potential to overcome the resistance of lung cancers to apoptosis.

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