2. Academic Validation
  3. Pseudolaric acid B suppresses NSCLC progression through the ROS/AMPK/mTOR/autophagy signalling pathway

Pseudolaric acid B suppresses NSCLC progression through the ROS/AMPK/mTOR/autophagy signalling pathway

  • Biomed Pharmacother. 2024 Apr 25:175:116614. doi: 10.1016/j.biopha.2024.116614.
Dan Luo 1,  Fang He 2,  Jingyun Liu 2,  Xueting Dong 2,  Mengying Fang 2,  Yuling Liang 2,  Mengqin Chen 2,  Xuemei Gui 2,  Wenjun Wang 2,  Li Zeng 3,  Xianming Fan 4,  Qibiao Wu 5
Affiliations

Affiliations

  • 1 Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China; Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China.
  • 2 Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China; Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China.
  • 3 Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China. Electronic address: Lzeng@must.edu.mo.
  • 4 Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China; Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China. Electronic address: fxm129@163.com.
  • 5 Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangdong, Guangzhou 510520, China; Zhuhai MUST Science and Technology Research Institute, Guangdong, Zhuhai 51900, China. Electronic address: qbwu@must.edu.mo.
PMID: 38670047 DOI: 10.1016/j.biopha.2024.116614
Abstract

Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the Anticancer effect of PAB on non-small cell lung Cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased Apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein LIGHT chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/p62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and p62 while decreasing the Apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited Autophagy and Apoptosis. Furthermore, PAB treatment increased intracellular Reactive Oxygen Species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with Autophagy and Apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce Apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.

Keywords

Adenosine 5’-monophosphate-activated protein kinase; Apoptosis; Autophagy; Non-small cell lung cancer; Pseudolaric acid B; Reactive oxygen species.

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