α-Hederin inhibits the growth of lung cancer A549 cells in vitro and in vivo by decreasing SIRT6 dependent glycolysis

Abstract Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.

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Molecular Role of EGFR-MAPK Pathway in Patchouli Alcohol-Induced Apoptosis and Cell Cycle Arrest on A549 CellsIn VitroandIn Vivo

BioMed Research International ◽

10.1155/2016/4567580 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

XinGang Lu ◽

Liu Yang ◽

ChengHua Lu ◽

ZhenYu Xu ◽

HongFu Qiu ◽

...

Keyword(s):

Lung Cancer ◽

Mapk Pathway ◽

A549 Cells ◽

Human Lung Cancer ◽

Activity Measurement ◽

Cover Glass ◽

Patchouli Alcohol ◽

Pogostemon Cablin

Nowadays, chemotherapy is still the main effective treatment for cancer. Herb prescriptions containingPogostemon cablin Benth(also known as “Guang-Huo-Xiang”) have been widely used in Chinese medicine today. In our research, we found that patchouli alcohol, a compound isolated from the oil ofPogostemon cablin Benth, exerted antitumor ability against human lung cancer A549 cells ability bothin vitroandin vivo. MTT assay was used to assess cell viability. Hoechst 33342 staining and TUNEL cover glass staining provided the visual evidence of apoptosis. Caspase activity measurement showed that patchouli alcohol activated caspase 9 and caspase 3 of mitochondria-mediated apoptosis. Consistently, patchouli alcohol inhibited the xenograft tumorin vivo. Further investigation of the underlying molecular mechanism showed that MAPK and EGFR pathway might contribute to the antitumor effect of patchouli alcohol. Our study proved that patchouli alcohol might be able to serve as a novel antitumor compound in the clinical treatment of lung cancer.

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Dendrobine Inhibits γ-Irradiation-Induced Cancer Cell Migration, Invasion and Metastasis in Non-Small Cell Lung Cancer Cells

Biomedicines ◽

10.3390/biomedicines9080954 ◽

2021 ◽

Vol 9 (8) ◽

pp. 954

Author(s):

Ye-Ram Kim ◽

Ah-Reum Han ◽

Jin-Baek Kim ◽

Chan-Hun Jung

Keyword(s):

Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Migration And Invasion ◽

Inhibitory Effects ◽

Invasion And Metastasis ◽

Small Cell Lung ◽

Γ Irradiation

The use of ionizing radiation (IR) during radiotherapy can induce malignant effects, such as metastasis, which contribute to poor prognoses in lung cancer patients. Here, we explored the ability of dendrobine, a plant-derived alkaloid from Dendrobium nobile, to improve the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). We employed Western blotting, quantitative real-time (qRT)-PCR, transwell migration assays, and wound-healing assays to determine the effects of dendrobine on the migration and invasion of A549 lung cancer cells in vitro. Dendrobine (5 mm) inhibited γ-irradiation-induced migration and invasion of A549 cells by suppressing sulfatase2 (SULF2) expression, thus inhibiting IR-induced signaling. To investigate the inhibitory effects of dendrobine in vivo, we established a mouse model of IR-induced metastasis by injecting BALB/c nude mice with γ-irradiated A549 cells via the tail vein. As expected, injection with γ-irradiated cells increased the number of pulmonary metastatic nodules in mice (0 Gy/DPBS, 9.8 ± 1.77; 2 Gy/DPBS, 20.87 ± 1.42), which was significantly reduced with dendrobine treatment (2 Gy/Dendrobine, 10.87 ± 0.71), by prevention of IR-induced signaling. Together, these findings demonstrate that dendrobine exerts inhibitory effects against γ-irradiation-induced invasion and metastasis in NSCLC cells in vitro and in vivo at non cytotoxic concentrations. Thus, dendrobine could serve as a therapeutic enhancer to overcome the malignant effects of radiation therapy in patients with NSCLC.

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PPy@Fe3O4 Nanoparticles Inhibit Tumor Growth and Metastasis Through Chemodynamic and Photothermal Therapy in Non-small Cell Lung Cancer

Frontiers in Chemistry ◽

10.3389/fchem.2021.789934 ◽

2021 ◽

Vol 9 ◽

Author(s):

Danruo Fang ◽

Hansong Jin ◽

Xiulin Huang ◽

Yongxin Shi ◽

Zeyu Liu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Photothermal Therapy ◽

Synergistic Effects ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung

Non-small cell lung cancer (NSCLC) is considered to be a principal cause of cancer death across the world, and nanomedicine has provided promising alternatives for the treatment of NSCLC in recent years. Photothermal therapy (PTT) and chemodynamic therapy (CDT) have represented novel therapeutic modalities for cancer treatment with excellent performance. The purpose of this research was to evaluate the effects of PPy@Fe3O4 nanoparticles (NPs) on inhibiting growth and metastasis of NSCLC by combination of PTT and CDT. In this study, we synthesized PPy@Fe3O4 NPs through a very facile electrostatic absorption method. And we detected reactive oxygen species production, cell apoptosis, migration and protein expression in different groups of A549 cells and established xenograft models to evaluate the effects of PPy@Fe3O4 NPs for inhibiting the growth of NSCLC. The results showed that the PPy@Fe3O4 NPs had negligible cytotoxicity and could efficiently inhibit the cell growth and metastasis of NSCLC in vitro. In addition, the PPy@Fe3O4 NPs decreased tumor volume and growth in vivo and endowed their excellent MRI capability of observing the location and size of tumor. To sum up, our study displayed that the PPy@Fe3O4 NPs had significant synergistic effects of PTT and CDT, and had good biocompatibility and safety in vivo and in vitro. The PPy@Fe3O4 NPs may be an effective drug platform for the treatment of NSCLC.

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Potential Analysis and Preparation of Chitosan Oligosaccharides as Oral Nutritional Supplements of Cancer Adjuvant Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms20040920 ◽

2019 ◽

Vol 20 (4) ◽

pp. 920 ◽

Cited By ~ 8

Author(s):

Zhiwen Jiang ◽

Hui Li ◽

Jing Qiao ◽

Yan Yang ◽

Yanting Wang ◽

...

Keyword(s):

Lung Cancer ◽

A549 Cells ◽

Food Ingredient ◽

Chitosan Oligosaccharides ◽

Lung Carcinoma Cells ◽

Human Liver Cell ◽

Oral Nutritional Supplements ◽

Fas L

Cancer is considered to have an adverse influence on health around the world. Chitosan, a linear polysaccharide that contains copolymers of β -1-4 linked d-glucosamine and N-acetyl-d-glucosamine units, has been widely used in the field of biomedicine, owing to its nontoxicity, biocompatibility, biodegradability, and hemocompatibility. This study was aimed at preparing the chitosan oligosaccharides (COS) and examining its ability on suppressing lung cancer in vitro and in vivo. Human non-small-cell lung cancer A549 cells model and C57BL/6 mice bearing lung cancer model were adopted. COS showed inhibition on the viability and proliferation of lung carcinoma cells (A549) in time-dependent manners, but no cytotoxicity to human liver cell (HL-7702). Moreover, COS could significantly increase Bax expression of A549 cells while decreasing Bcl-2 expression. COS supplementation significantly inhibited the growth of Lewis tissues and promoted necrosis of tumor cells in vivo. After treatment with COS, significantly elevated concentrations of Bax and reduced expression of Bcl-2 in tumor tissues, as well as elevated levels of TNF- α , IL-2, Fas and Fas-L in mice serum were observed (p < 0.05). In conclusion, COS had certain anti-tumor effects and potential application as a synergic functional food ingredient to prevent cancer.

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The synergistic antitumor effects of all-trans retinoic acid and C-phycocyanin on the lung cancer A549 cells in vitro and in vivo

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.01.009 ◽

2015 ◽

Vol 749 ◽

pp. 107-114 ◽

Cited By ~ 45

Author(s):

Bing Li ◽

Mei-Hua Gao ◽

Xian-Ming Chu ◽

Lei Teng ◽

Cong-Yi Lv ◽

...

Keyword(s):

Lung Cancer ◽

Retinoic Acid ◽

A549 Cells ◽

Antitumor Effects ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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Antitumor Activity of DFX117 by Dual Inhibition of c-Met and PI3Kα in Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers11050627 ◽

2019 ◽

Vol 11 (5) ◽

pp. 627 ◽

Cited By ~ 5

Author(s):

Yanhua Fan ◽

Huaiwei Ding ◽

Donghwa Kim ◽

Duc-Hiep Bach ◽

Ji-Young Hong ◽

...

Keyword(s):

Lung Cancer ◽

Antitumor Activity ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Pik3ca Mutation ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients.

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Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Cancers ◽

10.3390/cancers11010049 ◽

2019 ◽

Vol 11 (1) ◽

pp. 49 ◽

Cited By ~ 29

Author(s):

Young Yun Jung ◽

Muthu K. Shanmugam ◽

Acharan S. Narula ◽

Chulwon Kim ◽

Jong Hyun Lee ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Mouse Model ◽

A549 Cells ◽

Xenograft Model ◽

Signaling Cascade ◽

Anticancer Effects ◽

Anti Cancer

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

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Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis

Experimental Biology and Medicine ◽

10.1177/1535370218774737 ◽

2018 ◽

Vol 243 (9) ◽

pp. 739-748 ◽

Cited By ~ 7

Author(s):

Sei Won Kim ◽

In Kyoung Kim ◽

Jick Hwan Ha ◽

Chang Dong Yeo ◽

Hyeon Hui Kang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

A549 Cells ◽

Migration And Invasion ◽

Control Group ◽

Normobaric Hyperoxia ◽

Human Lung Cells ◽

Hyperoxia Exposure

Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks. In addition, A549 lung cancer cells were incubated in a normobaric hyperoxia chamber for a 24-h period. As a result, the size and number of tumors in the lung decreased significantly with exposure to normobaric hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric hyperoxia and the normal control group exposed to normobaric hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric hyperoxia in cancer cells. A549 cells exposed to normobaric hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2 mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric hyperoxia in inhibiting lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-tumor effect of normobaric hyperoxia may due to the increased reactive oxygen species activity and apoptosis, which is related to the mitogen-activated protein kinase pathway. Impact statement Normobaric hyperoxia (NBO) is a feasible therapy for cancer with a low complication rate. Although NBO may be beneficial in cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.

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