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

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

  • J Integr Med. 2024 May 24:S2095-4964(24)00335-2. doi: 10.1016/j.joim.2024.05.004.
Li-Hua Zhu 1,  Yu-Pei Liang 2,  Lian Yang 3,  Feng Zhu 4,  Li-Jun Jia 5,  He-Gen Li 6
Affiliations

Affiliations

  • 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.
  • 5 Cancer Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: ljjia@shutcm.edu.cn.
  • 6 Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: shlaogen@163.com.
PMID: 38849220 DOI: 10.1016/j.joim.2024.05.004
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 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 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: Epub ahead of print.

Keywords

Apoptosis; Autophagy; Cycloastragenol; Non-small cell lung cancer.

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