1. Academic Validation
  2. Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic flux in human osteosarcoma cells

Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic flux in human osteosarcoma cells

  • Phytomedicine. 2018 Mar 15;42:190-198. doi: 10.1016/j.phymed.2018.03.046.
Hua Lin 1 Chao Zhang 1 Hao Zhang 1 Yuan-Zheng Xia 1 Chuan-Yang Zhang 1 Jie Luo 1 Lei Yang 2 Ling-Yi Kong 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
  • 2 Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: yanglei@cpu.edu.cn.
  • 3 Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: cpu_lykong@126.com.
Abstract

Background: Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown.

Purpose: To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms.

Methods: Cell viability was measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP), Reactive Oxygen Species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry. Protein levels were analyzed by immunofluorescence and western blotting.

Results: PG inhibited cell proliferation and induced Apoptosis in human osteosarcoma cells. PG treatment blocked EGFR phosphorylation and suppressed epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as Akt and mTOR. PG treatment resulted in lysosome dysfunction by altering lysosome acidification and LAMP1 levels, which led to autophagosome accumulation and autophagic flux inhibition.

Conclusion: PG inhibits cell proliferation and EGFR/mTOR signaling in human osteosarcoma cells. Moreover, PG induces Apoptosis through the mitochondrial pathway and impedes autophagic flux via lysosome dysfunction. Our findings indicate that PG has the potential to play a significant role in the treatment of osteosarcoma.

Keywords

Apoptosis; Autophagy; EGFR/mTOR; Osteosarcoma; Physakengose G.

Figures
Products