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 BA6 Induces Apoptosis via Stimulation of Reactive Oxygen Species and Inhibition of Oxidative Phosphorylation in Human Lung Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Meng-Hsuan Cheng ◽  
Hung-Ling Huang ◽  
Yen-You Lin ◽  
Kuan-Hao Tsui ◽  
Pei-Chin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Induced Apoptosis

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.

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.

scholarly journals Tetrazolium Violet Induced Apoptosis and Cell Cycle Arrest in Human Lung Cancer A549 Cells

2012 ◽  
Vol 20 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Xiao-Hong Zhang ◽  
Nan Zhang ◽  
Jian-Mei Lu ◽  
Qing-Zhong Kong ◽  
Yun-Feng Zhao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Cycle Arrest ◽  
Tetrazolium Violet ◽  
Induced Apoptosis

Naringenin up-regulates the expression of death receptor 5 and enhances TRAIL-induced apoptosis in human lung cancer A549 cells

2011 ◽  
Vol 55 (2) ◽  
pp. 300-309 ◽  
Author(s):  
Cheng-Yun Jin ◽  
Cheol Park ◽  
Hye Jin Hwang ◽  
Gi-Young Kim ◽  
Byung Tae Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Death Receptor ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Death Receptor 5 ◽  
Induced Apoptosis

scholarly journals Swainsonine Activates Mitochondria-mediated Apoptotic Pathway in Human Lung Cancer A549 Cells and Retards the Growth of Lung Cancer Xenografts

2012 ◽  
Vol 8 (3) ◽  
pp. 394-405 ◽  
Author(s):  
Zhaocai Li ◽  
Xingang Xu ◽  
Yong Huang ◽  
Li Ding ◽  
Zhisheng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Apoptotic Pathway

Brazilian green propolis induced apoptosis in human lung cancer A549 cells through mitochondrial-mediated pathway

2015 ◽  
Vol 67 (10) ◽  
pp. 1448-1456 ◽  
Author(s):  
Yahima Frión-Herrera ◽  
Alexis Díaz-García ◽  
Jenny Ruiz-Fuentes ◽  
Hermis Rodríguez-Sánchez ◽  
José Maurício Sforcin
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Induced Apoptosis ◽  
Brazilian Green Propolis

scholarly journals Chrysin Sensitizes Human Lung Cancer Cells to Tumour Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) Mediated Apoptosis

2019 ◽  
Vol 4 (2) ◽  
pp. 27-33
Author(s):  
Syed Hassan Mehdi ◽  
Md Zafaryab ◽  
Sana Nafees ◽  
Asad Khan ◽  
Irfan Ahmad ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Caspase 3 ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Induced Apoptosis ◽  
Necrosis Factor

Background: Lung cancer is the primary cause of cancer deaths worldwide. Thus, the requisite for more coherent methods to lung cancer therapy is needed. Purpose: Chrysin (5, 7-dihydroxyflavone) is a naturally occurring flavonoid having a wide range of pharmacological properties and is commonly found in fruits, vegetables, honey and propolis. In our study, we have hypothesized that chrysin would have anticancer activity on L132 lung cancer cell line.Methods: The cytotoxic effects were assessed by MTT and NRU assay. DAPI was used to evaluate the cell death. The pro- or anti-apoptotic proteins were detected by Western Blot assay, and, besides, mRNA expression was analysed with RT-PCR. In silico study of chrysin was performed to identify suitable inhibitors against the protein function. Results: Results indicated that chrysin enhanced the inhibitory effects of TRAIL (Tumour Necrosis Factor Related Apoptosis-Inducing Ligand) in comparison to TNF-α (tumour necrosis factor) on cell viability in L132 lung cancer cells and altered nuclear morphology of cells was observed in DAPI (4’,6-diamidino-2-phenylindole) staining after 48 hrs treatment. Treatment with chrysin enhances TRAIL-induced apoptosis by increasing the expression of apoptosis-related proteins including caspase-3, 8, 9 and Bax, whereas the expression of Bcl-2 was decreased. Chrysin was docked with caspase-3, 8, 9, Bax, and Bcl-2 proteins to identify suitable inhibitors against the protein function.Conclusion: We concluded that chrysin sensitizes lung cancer cells to TRAIL-induced apoptosis and may be considered for future studies as a promising therapeutic candidate for human lung cancer.

Inhibitory effect of lignans from Ailanthus altissima on proliferation of human lung cancer cells and its mechanism.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15059-e15059
Author(s):  
Yu Wang ◽  
Siming Wang ◽  
Yibing Wu ◽  
Mei Dong ◽  
Zhiyu Ni
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Human Lung ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
Human Lung Cancer ◽  
Ailanthus Altissima ◽  
Control Group ◽  
Caspase Inhibitor ◽  
Significant Difference

e15059 Background: Plants are thought to contain compounds that inhibit the proliferation of cancer cells in vitro, and many attempts have been made to isolate anti-cancer drugs from plants. Ailanthus altissima is a family of Simaroubaceae, the bark is gray to grayish-black, because of the smell of the gland patches at the base of the leaves. 3,5,3-trimethoxy-8,1-neoligna-4,2,7,9,9-pentol (TNP) isolated from Ailanthus altissima. Methods: (1) Apoptosis was detected by flow cytometry: the cells were incubated with 10 mmol/L TNP for 24 h, and the cells were collected. The cell concentration was adjusted to 5×105 ̃ 5×106/ L. While propionate iodide was added for DNA fluorescence staining (Propidium Iodide, PI: 50 mg/L，triton-x100 1.0%). (2) The changes of p53, Bax and caspase-3 were detected by Western blot. The cells were cultured in 10 μmol/L cisplatin and TNP medium for 24 hours. Image J image analysis software is used for semi quantitative analysis. The data were expressed by mean standard deviation, and the mean values of each group were compared by analysis of variance and the least significant difference. There was a significant difference in P< 0.05. (3) A549 cells were treated with 10 μmol/L cisplatin and TNP. A549 cells were incubated with cisplatin and TNP, and then treated with solvent control (final concentration 0.1% dimethyl sulfoxide) with or without caspase inhibitor for 48 hours The OD value was determined by MTT method. Cell survival rate (%) = (OD value of control group /OD value of control group) 100%. Results: (1) The reverse effect of caspase inhibitor on the proliferation of A549 cells: the cell survival rates of A549 cells treated with 0.1, 1 and 10 μmol/L cisplatin and TNP were 96.11%, 72.36%, 27.57% and 71.42%, 28.97% and 4.34% respectively. The survival rate of A549 cells incubated with cisplatin and TNP 20 μmol/L increased to 100.00%, 81.92%, 57.54% and 85.69%, 48.57% and 16.95% respectively. Caspase inhibitor reversed the inhibitory effect of TNP on A549 cells. (2) The effect of TNP on apoptosis of A549 cells: after treatment with 10 μmol/L TNP for 24 h, the apoptosis rate of A549 cells was (24.01)%, which was significantly higher than that of the blank control group (6.79)% ( P< 0.05). (3) The results showed that the up regulation of p53, Bax and caspase-3 protein by TNP was 10 μmol/L. Conclusions: TNP can induce apoptosis of human lung cancer cell line A549, and it can up regulate the expression of p53, Bax and Caspase-3, which may be one of the mechanisms of TNP inducing apoptosis of A549 cells. The experiment also proves that caspase inhibitor can reverse the effect of TNP. TNP inhibits the proliferation of A549 cells.

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