Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits growth of human lung cancer A549 cells by arresting cell cycle and triggering apoptosis

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.

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

Biomolecules & Therapeutics ◽

10.4062/biomolther.2012.20.2.177 ◽

2012 ◽

Vol 20 (2) ◽

pp. 177-182 ◽

Cited By ~ 4

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

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Cell Cycle Arrest and Cytochrome C-mediated Apoptotic Induction in Human Lung Cancer A549 Cells by MCS-C2, an Analogue of Sangivamycin

Journal of Microbiology and Biotechnology ◽

10.4014/jmb.0910.10010 ◽

2010 ◽

Vol 20 (2) ◽

pp. 428-432 ◽

Cited By ~ 3

Author(s):

Jeonghwa Kang ◽

Dong-Keun Lee ◽

Chul-Hoon Lee

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cytochrome C ◽

Cell Cycle Arrest ◽

Human Lung ◽

A549 Cells ◽

Human Lung Cancer ◽

Cycle Arrest ◽

Apoptotic Induction

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Kaempferide Induces G0/G1 Phase Arrest and Apoptosis via ROS-Mediated Signaling Pathways in A549 Human Lung Cancer Cells

Natural Product Communications ◽

10.1177/1934578x20935226 ◽

2020 ◽

Vol 15 (7) ◽

pp. 1934578X2093522

Author(s):

Hong-Liang Li ◽

Shu-Mei Li ◽

Ying-Hua Luo ◽

Wan-Ting Xu ◽

Yu Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Signaling Pathways ◽

Cell Apoptosis ◽

Human Lung ◽

A549 Cells ◽

Human Lung Cancer ◽

Expression Levels ◽

Cycle Arrest ◽

Human Lung Cancer Cells

Kaempferide is an O-methylated flavonol that has received much attention due to its various biological activities. In this study, we explored the underlying mechanisms of kaempferide in human lung cancer A549 cells. The Cell Counting Kit-8 (CCK-8) assay, Hoechst 33342/propidium iodide double staining, flow cytometry, scratch wound healing assay, and Western blot analysis were used to measure cell apoptosis, the cell cycle, reactive oxygen species (ROS) levels, and cell migration of human lung cancer cells. Kaempferide significantly inhibited human lung cancer cell proliferation, and its toxic effects on normal cells were significantly lower than those of 5-fluorouracil. Kaempferide induced A549 cell apoptosis by decreasing the mitochondrial membrane potential and the expression level of B-cell lymphoma 2, and by increasing the expression levels of Bcl-2-associated X protein and caspase-3. It also regulated mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) signaling pathways by increasing the expression levels of phosphorylated c-Jun N-terminal kinase, p-p38, I kappa B, and by decreasing the expression levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, and NF-κB. Kaempferide induced cell cycle arrest in the G0/G1 phase in A549 cells by downregulating the expression levels of p-AKT, cyclin D1, and cyclin-dependent kinase 2. Furthermore, kaempferide blocked A549 cell migration by downregulating the expression levels of transforming growth factor beta 1 (TGF-β1), p-β-catenin, p-glycogen synthase kinase 3 beta, N-cadherin, and vimentin, and by upregulating the expression level of E-cadherin. Kaempferide enhanced the accumulation of ROS, and N-acetyl-l-cysteine (a ROS inhibitor) decreased the regulation of MAPK, NF-κB, AKT, and TGF-β signaling pathways by kaempferide, inhibited cell apoptosis, and reversed cell cycle arrest. Our results showed that kaempferide induced apoptosis via ROS-mediated MAPK, NF-κB, AKT, and TGF-β signaling pathways in A549 cells. Thus, kaempferide may be a novel drug candidate for lung cancer.

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Auricularia polytricha polysaccharides induce cell cycle arrest and apoptosis in human lung cancer A549 cells

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2014.04.018 ◽

2014 ◽

Vol 68 ◽

pp. 67-71 ◽

Cited By ~ 25

Author(s):

Jie Yu ◽

Ruilin Sun ◽

Zhongquan Zhao ◽

Yingyu Wang

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Human Lung ◽

A549 Cells ◽

Human Lung Cancer ◽

Induce Cell Cycle Arrest ◽

Auricularia Polytricha ◽

Cycle Arrest

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HY253, a novel decahydrofluorene analog, from Aralia continentalis, induces cell cycle arrest at the G1 phase and cytochrome c-mediated apoptosis in human lung cancer A549 cells

Journal of Ethnopharmacology ◽

10.1016/j.jep.2010.02.010 ◽

2010 ◽

Vol 129 (1) ◽

pp. 135-139 ◽

Cited By ~ 12

Author(s):

Ha Lim Oh ◽

Dong-Keun Lee ◽

Haeyoung Lim ◽

Chul-Hoon Lee

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cytochrome C ◽

Cell Cycle Arrest ◽

Human Lung ◽

A549 Cells ◽

Human Lung Cancer ◽

G1 Phase ◽

Aralia Continentalis ◽

Cycle Arrest

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NBM-T-BMX-OS01, an Osthole Derivative, Sensitizes Human Lung Cancer A549 Cells to Cisplatin through AMPK-Dependent Inhibition of ERK and Akt Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000430264 ◽

2015 ◽

Vol 36 (3) ◽

pp. 893-906 ◽

Cited By ~ 6

Author(s):

Tian-Jun Chen ◽

Yue-Fei Zhou ◽

Jie-Juan Ning ◽

Tian Yang ◽

Hui Ren ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Colony Formation ◽

Human Lung ◽

Cisplatin Resistance ◽

A549 Cells ◽

Human Lung Cancer ◽

Ros Generation ◽

Fluorescence Staining ◽

Inhibition Of Proliferation

Background: Drug combination therapies using cisplatin and natural products are common practice in the treatment of human lung cancer. Osthole is a natural compound extracted from a number of medicinal plants and has been shown to exert strong anticancer activities with low toxicity. Methods: In the present study, NBM-T-BMX-OS01 (BMX), derived from the semi-synthesis of osthole, was evaluated in cisplatin treated A549 cells to investigate its effect on cisplatin resistance in human lung cancer. The anticancer effect of BMX were measured by cell viablity‚ colony formation‚ TUNEL staining‚ flow cytometry and cell cycle assay. The fluorescence staining was performed to detect intracellular and mitochondrial reactive oxygen species (ROS) generation. Western blot analysis, antagonists pretreatment and small interfering RNA (siRNA) transfection were used to determine the potential mechanism. Results: It was found that, in comparison with single cisplatin treatment, the combination of BMX and cisplatin resulted in greater efficacy in inhibition of proliferation and colony formation, apoptosis induction and cell cycle arrest. The results of fluorescence staining showed that the combination effect of BMX and cisplatin was due to oxidative stress induced by mitochondrial ROS generation. In addition, BMX significantly attenuated the phosphorylation of ERK and Akt, two important pro-survival kinases. In contrast, BMX inhibited the activation of AMPK, and knockdown of AMPK using specific siRNA partially reversed BMX-induced inhibition of ERK and Akt, as well as its synthetic effects on cisplatin induced anticancer activity in A549 cells. Conclusion: Taken together, this study provides that BMX might modulate cisplatin resistance through AMPK-ERK and AMPK-Akt pathways. These results also support the role of BMX as a potential drug candidate for use in combination with cisplatin in the treatment of human lung cancer.

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