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

Li-hua Zhu ¹Yu-pei Liang ²Lian Yang ³Feng Zhu ⁴Li-jun Jia ²He-gen Li³

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作者信息

1. Department of Oncology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Cancer Institute of Traditional Chinese Medicine,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China
2. Cancer Institute of Traditional Chinese Medicine,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China
3. Department of Oncology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China
4. Department of Laboratory Medicine,Huadong Hospital,Fudan University,Shanghai 200237,China
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Abstract

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate,colorec-tal 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 adeno-sine 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 cycloas-tragenol 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 5'-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 cycloas-tragenol 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.

Key words

Non-small cell lung cancer/Cycloastragenol/Autophagy/Apoptosis

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基金项目

following funds:National Natural Science Foundation of China(82205214)

following funds:National Natural Science Foundation of China(82374532)

following funds:National Natural Science Foundation of China(81820108022)

following funds:National Natural Science Foundation of China(82002973)

National Key R&D Program of China(2022YFC3500200)

National Key R&D Program of China(2022YFC3500202)

Shanghai"Science and Technology Innovation Action Plan"Medical Innovation Research Project(21MC1930500)

出版年

2024

结合医学学报(英文版)

上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCDCSCD

影响因子：0.711

ISSN：2095-4964

参考文献量37

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