Discovery of new fluorescent thiazole–pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells

AbstractA series of fluorescent thiazole–pyrazoline derivatives was synthesized and their structures were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure–activity relationship (SAR) of the compounds was analyzed. Further mechanism research revealed they could induce autophagy and cell cycle arrest while had no influence on cell necrosis. Compound 5e inhibited the activity of mTOR via FKBP12, which could be reversed by 3BDO, an mTOR activator and autophagy inhibitor. Compound 5e inhibited growth, promoted autophagy of A549 cells in vivo. Moreover, compound 5e showed good selectivity with no influence on normal vascular endothelial cell growth and the normal chick embryo chorioallantoic membrane (CAM) capillary formation. Therefore, our research provides potential lead compounds for the development of new anticancer drugs against human lung cancer.

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In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells

Biochemical Pharmacology ◽

10.1016/j.bcp.2006.04.031 ◽

2006 ◽

Vol 72 (3) ◽

pp. 308-319 ◽

Cited By ~ 58

Author(s):

Yi-Lin Chen ◽

Shinn-Zong Lin ◽

Jang-Yang Chang ◽

Yeung-Leung Cheng ◽

Nu-Man Tsai ◽

...

Keyword(s):

Lung Cancer ◽

Anticancer Agent ◽

Human Lung ◽

A549 Cells ◽

In Vivo Studies ◽

Human Lung Cancer

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POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01476-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ronggang Luo ◽

Yi Zhuo ◽

Quan Du ◽

Rendong Xiao

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

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Functional Gene Knockout of NRF2 Increases Chemosensitivity of Human Lung Cancer A549 Cells In Vitro and in a Xenograft Mouse Model

Molecular Therapy — Oncolytics ◽

10.1016/j.omto.2018.10.002 ◽

2018 ◽

Vol 11 ◽

pp. 75-89 ◽

Cited By ~ 11

Author(s):

Pawel Bialk ◽

Yichen Wang ◽

Kelly Banas ◽

Eric B. Kmiec

Keyword(s):

Lung Cancer ◽

Mouse Model ◽

Human Lung ◽

Gene Knockout ◽

A549 Cells ◽

Functional Gene ◽

Human Lung Cancer ◽

Xenograft Mouse Model

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Cytotoxic Effects of Flubendazole in Human Lung Cancer Cell Line A549

Jentashapir Journal of Cellular and Molecular Biology ◽

10.5812/jjcmb.108923 ◽

2020 ◽

Vol 11 (4) ◽

Author(s):

Elham Hoveizi ◽

Fatemeh Fakharzadeh Jahromi

Keyword(s):

Lung Cancer ◽

Cell Viability ◽

Human Lung ◽

A549 Cells ◽

Beclin 1 ◽

Human Lung Cancer ◽

Pcr Analysis ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Acridine Orange Staining

Background: The development of effective anticancer drugs is a significant health issue. Previous studies showed that members of the benzimidazole family have anticancer effects on several cancers Objectives: The present study investigated the cytotoxic effect of flubendazole on A549 human lung cancer cells. Methods: The A549 cells were treated with flubendazole at 1, 2, 5, and 10 µM concentrations for three days. Cell viability was measured by the MTT assay and Acridine orange staining. Also, the expressions of P62 and Beclin -1 were analyzed by qRT-PCR analysis. Results: Cell viability of A549 cells, in a concentration-dependent manner, showed significant differences between the treatment and control groups, and the IC50 value was determined to be 2 µM. Also, flubendazole reduced the expression of P62 and increased the expression of Beclin 1 in treated cells. Conclusions: Flubendazole induces cell death in A549 cells in a dose and time-dependent manner and can offer new factors in lung cancer therapeutic strategies.

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Bicistronic transfer of CDKN2A and p53 culminates in collaborative killing of human lung cancer cells in vitro and in vivo

Gene Therapy ◽

10.1038/s41434-019-0096-1 ◽

2019 ◽

Vol 27 (1-2) ◽

pp. 51-61

Author(s):

Juliana G. Xande ◽

Ana P. Dias ◽

Rodrigo E. Tamura ◽

Mario C. Cruz ◽

Bárbara Brito ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells

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Effect of Compound K, a Metabolite of Ginseng Saponin, Combined with γ-Ray Radiation in Human Lung Cancer Cells in Vitro and in Vivo

Journal of Agricultural and Food Chemistry ◽

10.1021/jf900331g ◽

2009 ◽

Vol 57 (13) ◽

pp. 5777-5782 ◽

Cited By ~ 83

Author(s):

Sungwook Chae ◽

Kyoung Ah Kang ◽

Weon Young Chang ◽

Min Jung Kim ◽

Su Jae Lee ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Human Lung Cancer ◽

Compound K ◽

Ginseng Saponin ◽

Human Lung Cancer Cells ◽

Γ Ray

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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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Extract from the Leaves of Toona sinensis Roemor Exerts Potent Antiproliferative Effect on Human Lung Cancer Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x02000223 ◽

2002 ◽

Vol 30 (02n03) ◽

pp. 307-314 ◽

Cited By ~ 46

Author(s):

Hui-Chiu Chang ◽

Wen-Chun Hung ◽

Ming-Shyan Huang ◽

Hseng-Kuang Hsu

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Apoptotic Cell ◽

A549 Cells ◽

Lung Cancer Cells ◽

Lung Fibroblasts ◽

Human Lung Cancer ◽

Toona Sinensis

Recent study indicated that the components of Toona sinensis Roemor have potent anti-inflammatory and analgesic effects. These components have also been reported to inhibit the growth of boils in vivo. In this study, we investigated the effect of crude extract from the leaves of Toona sinensis Roemor on the proliferation of A549 lung cancer cells. We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells. Additionally, incubation of the extract led to activation of caspase-3-like proteases and apoptotic cell death. Conversely, the extract did not show any significant cytotoxic effect on primarily cultured human foreskin fibroblasts or MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract is specific for tumor cells. Our results suggest that the components of Toona sinensis Roemor have potent anticancer effects in vitro and identification of the useful components in the extract may lead to the development of a novel class of anticancer drugs.

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