Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

IF 4.2 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
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引用次数: 0

Abstract

Objective

Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer (NSCLC) and elucidates the underlying molecular mechanisms.

Methods

The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays. Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots. Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology, were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.

Results

Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1 (NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5ʹ-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.

Conclusion

Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

Please cite this article as follows: Zhu LH, Liang YP, Yang L, Zhu F, Jia LJ, Li HG. Cycloastragenolinduces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small celllung cancer cell lines. J Integr Med. 2024; 22(4): 504–515.

环黄芪醇通过 AMPK/ULK1/mTOR 轴诱导人非小细胞肺癌细胞株凋亡和保护性自噬
目的研究表明,环黄芪醇可诱导前列腺癌、结直肠癌和胃癌的抗肿瘤作用,但其抑制肺癌细胞增殖的功效却尚未得到广泛探讨。本研究探讨了环黄芪醇抑制非小细胞肺癌(NSCLC)的功效,并阐明了其潜在的分子机制。方法使用基于萤火虫荧光素酶和克隆形成试验的三磷酸腺苷监测系统评估环黄芪醇对肺癌细胞增殖的影响。使用附件素 V-异硫氰酸荧光素/碘化丙啶试剂盒的双重染色流式细胞术评估了环黄芪醇诱导的肺癌细胞凋亡。为了阐明环黄芪醇在诱导细胞凋亡中的作用,使用 Western 印迹法检测了与细胞凋亡相关的蛋白质。免疫荧光和 Western 印迹技术用于确定环黄芪醇是否能诱导肺癌细胞自噬。基因技术,包括小干扰 RNA 技术,被用来研究其潜在机制。利用小鼠皮下肿瘤模型评估了环黄芪醇对肺癌的作用和生物安全性。具体来说,环黄芪醇通过促进光甘油-12-肉豆蔻酸-13-乙酸诱导蛋白1(NOXA)的积累来促进细胞凋亡,NOXA是一种关键的细胞凋亡相关蛋白。此外,环黄芪醇通过调节腺苷-5ʹ-单磷酸激活蛋白激酶(AMPK)/unc-51样自噬激活激酶(ULK1)/哺乳动物雷帕霉素靶标(mTOR)通路,诱导保护性自噬反应。这一发现为探索环黄芪醇与抑制AMPK/ULK1/mTOR通路的联合疗法提供了科学依据,是一种很有前景的抗击肺癌的方法:Zhu LH, Liang YP, Yang L, Zhu F, Jia LJ, Li HG.环黄芪醇通过AMPK/ULK1/mTOR轴在人非小细胞肺癌细胞系中诱导凋亡和保护性自噬。J Integr Med.2024; 22(4):504-515.
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来源期刊
Journal of Integrative Medicine-Jim
Journal of Integrative Medicine-Jim Medicine-Complementary and Alternative Medicine
CiteScore
9.20
自引率
4.20%
发文量
3319
期刊介绍: The predecessor of JIM is the Journal of Chinese Integrative Medicine (Zhong Xi Yi Jie He Xue Bao). With this new, English-language publication, we are committed to make JIM an international platform for publishing high-quality papers on complementary and alternative medicine (CAM) and an open forum in which the different professions and international scholarly communities can exchange views, share research and their clinical experience, discuss CAM education, and confer about issues and problems in our various disciplines and in CAM as a whole in order to promote integrative medicine. JIM is indexed/abstracted in: MEDLINE/PubMed, ScienceDirect, Emerging Sources Citation Index (ESCI), Scopus, Embase, Chemical Abstracts (CA), CAB Abstracts, EBSCO, WPRIM, JST China, Chinese Science Citation Database (CSCD), and China National Knowledge Infrastructure (CNKI). JIM Editorial Office uses ThomsonReuters ScholarOne Manuscripts as submitting and review system (submission link: http://mc03.manuscriptcentral.com/jcim-en). JIM is published bimonthly. Manuscripts submitted to JIM should be written in English. Article types include but are not limited to randomized controlled and pragmatic trials, translational and patient-centered effectiveness outcome studies, case series and reports, clinical trial protocols, preclinical and basic science studies, systematic reviews and meta-analyses, papers on methodology and CAM history or education, conference proceedings, editorials, commentaries, short communications, book reviews, and letters to the editor. Our purpose is to publish a prestigious international journal for studies in integrative medicine. To achieve this aim, we seek to publish high-quality papers on any aspects of integrative medicine, such as acupuncture and traditional Chinese medicine, Ayurveda medicine, herbal medicine, homeopathy, nutrition, chiropractic, mind-body medicine, taichi, qigong, meditation, and any other modalities of CAM; our commitment to international scope ensures that research and progress from all regions of the world are widely covered. These ensure that articles published in JIM have the maximum exposure to the international scholarly community. JIM can help its authors let their papers reach the widest possible range of readers, and let all those who share an interest in their research field be concerned with their study.
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