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  2. Phytosphingosine inhibits the growth of lung adenocarcinoma cells by inducing G2/M-phase arrest, apoptosis, and mitochondria-dependent pathway cell death in vitro and in vivo

Phytosphingosine inhibits the growth of lung adenocarcinoma cells by inducing G2/M-phase arrest, apoptosis, and mitochondria-dependent pathway cell death in vitro and in vivo

  • Chem Biol Interact. 2024 Jan 5:387:110795. doi: 10.1016/j.cbi.2023.110795.
Qi Cai 1 Min Chen 2 Bo Wang 3 Jin Wang 4 Lijie Xia 5 Jinyao Li 6
Affiliations

Affiliations

  • 1 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China. Electronic address: caiqi@stu.xju.edu.cn.
  • 2 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China. Electronic address: 467115540@qq.com.
  • 3 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China. Electronic address: wbxjhyj@aliyun.com.
  • 4 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China. Electronic address: wangjin5020@163.com.
  • 5 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China. Electronic address: xlj@xju.edu.cn.
  • 6 Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China. Electronic address: ljyxju@xju.edu.
Abstract

In order to search for novel antitumor drugs with high efficiency and low toxicity, the anti-lung Cancer activity of phytosphingosine was studied. Phytosphingosine is widely distributed in fungi, Plants, Animals, and has several biological activities, including anti-inflammation and anti-tumor. However, its anti-lung Cancer activity needs to be further investigated. The effects and pharmacological mechanisms of phytosphingosine on lung Cancer treatment were investigated both in vitro and in vivo. The results showed that phytosphingosine inhibited the growth of lung Cancer cell lines. Phytosphingosine induced Apoptosis through a mitochondria-mediated pathway, phytosphingosine arrested the cell cycle at the G2/M phase and induced Apoptosis in a dose-dependent manner by increasing Bax/Bcl-2 ratio, which caused the decrease of mitochondrial membrane potential to promote the release of cytochrome C, Caspase 9 and 3, and degrade PARP in A549 cells. The results showed that phytosphingosine could damage the mitochondrial functions, increase ROS levels, and arrest the cell cycle at the G2/M stages. Finally, phytosphingosine also inhibited the growth of tumor in mice. Taken together, phytosphingosine suppressed the growth of lung Cancer cells both in vitro and in vivo and had potential application in the research and development of antitumor drugs. The aim of the present study was to explain the theoretical basis of phytosphingosine therapy for lung Cancer and providing new possibilities for lung Cancer treatment.

Keywords

Cell cycle arrest; Lung cancer; Mitochondrial apoptosis pathway; Phytosphingosine; Reactive oxygen species (ROS).

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