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

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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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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Targeted Photodynamic Therapy (PDT) of Lung Cancer with Biotinylated Silicon (IV) Phthalocyanine.

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200510001627 ◽

2020 ◽

Vol 21 ◽

Author(s):

Wenyi Dong ◽

Ke Li ◽

Shijie Wang ◽

Ling Qiu ◽

Qingzhu Liu ◽

...

Keyword(s):

Lung Cancer ◽

Photodynamic Therapy ◽

Imaging System ◽

A549 Cells ◽

Human Lung Cancer ◽

In Vitro Assays ◽

Cancer Therapies ◽

Lung Cancers

Background: Lung cancer is the leading cause of cancer-associated mortality in the world. Traditional cancer therapies prolong life expectancy of patients but often suffer from adverse reactions. Photodynamic therapy (PDT) has been recommended as a treatment option for lung cancer in several countries, due to its non-invasive procedures, high selectivity and weak side effects. Objective: We have designed and synthesized a biotin receptor-targeted silicon phthalocyanine (IV) (compound 1) which showed good therapeutic effect on biotin receptor-positive tumors. Since the overexpression of biotin receptor (BR) is also present in human lung cancer cells (A549), we explored the therapeutic properties of compound 1 on A549 xenograft tumor models. Method: The selectivity of compound 1 toward A549 cells was studied with fluorescence microscope and IVIS Spectrum Imaging System. The cytotoxicity was measured using MTT assay. In vivo anti-tumor activity was investigated on the nude mice bearing A549 xenografts. Results: In vitro assays proved that compound 1 could selectively accumulate in A549 cells via the BR-mediated internalization. In vivo imaging and distribution experiments showed that compound 1 could selectively accumulate in tumor tissues of tumor-bearing mice. After 16 days of the treatment, the volumes of tumor in PDT group were obviously smaller than that in other groups. Conclusion: This study demonstrates that compound 1 is a promising photosensitizer and has broad application prospects in clinical PDT of lung cancers.

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

Cell Death and Disease ◽

10.1038/s41419-020-02746-w ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 2

Author(s):

ZhaoMin Lin ◽

ZhaoYang Wang ◽

XueWen Zhou ◽

Ming Zhang ◽

DongFang Gao ◽

...

Keyword(s):

Lung Cancer ◽

Human Lung ◽

Vascular Endothelial Cell ◽

Chorioallantoic Membrane ◽

A549 Cells ◽

Biological Evaluation ◽

Human Lung Cancer ◽

Dependent Manner

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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Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway

Biological Research ◽

10.1186/s40659-021-00330-w ◽

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.

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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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