2. Academic Validation
  3. Berberine-photodynamic therapy sensitizes melanoma cells to cisplatin-induced apoptosis through ROS-mediated P38 MAPK pathways

Berberine-photodynamic therapy sensitizes melanoma cells to cisplatin-induced apoptosis through ROS-mediated P38 MAPK pathways

  • Toxicol Appl Pharmacol. 2021 May 1;418:115484. doi: 10.1016/j.taap.2021.115484.
Xiaotong Wang 1,  Qianyi Gong 1,  Changfeng Song 1,  Jiaping Fang 1,  Yun Yang 2,  Xin Liang 3,  Xuan Huang 4,  Jianwen Liu 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
  • 2 Department of Pharmacy, School of Medicine, Jiaxing University, Jiaxing, Zhejiang 314001, China.
  • 3 State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: xin.liang@ecust.edu.cn.
  • 4 Department of Pharmacy, School of Medicine, Jiaxing University, Jiaxing, Zhejiang 314001, China; Natural Medicine and Health Food Research & Technology Innovation Team of Jiaxing, Jiaxing, Zhejiang 314001, China; Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research, China. Electronic address: waynett2021@126.com.
  • 5 State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: liujian@ecust.edu.cn.
PMID: 33716044 DOI: 10.1016/j.taap.2021.115484
Abstract

The clinical use of cisplatin are limited due to its drug resistance. Thus, it is urgent to find effective combination therapy that sensitizes tumor cells to this drug. The combined chemo-photodynamic therapy could increase anti-tumor efficacy while also reduce the side effects of cisplatin. Berberine is an isoquinoline alkaloid, which has been reported to show high photosensitizing activity. In this study, we have examined the effect of a combination of cisplatin and berberine-PDT in cisplatin-resistant melanoma cells. The cytotoxic effects of berberine-PDT alone or in combination with cisplatin were tested by MTT assays. We then examined the subcellular localization of berberine with confocal fluorescence microscopy. The percentage of apoptotic cells, the mitochondrial membrane potential (Δψm) and Reactive Oxygen Species (ROS) generation assessed using flow cytometry analysis. Western blotting used in this study to determine the expression levels of MAPK signaling pathways and apoptosis-related proteins. Experimental data revealed that the mode of cell death is the caspase-dependent mitochondrial apoptotic pathways. Excessive accumulation of ROS played a key role in this process, which is confirmed by alleviation of cytotoxicity upon pretreatment with NAC. Furthermore, we found that the combined treatment activated MAPK signaling pathway. The inhibition of p38 MAPK by pretreating with SB203580 block the combined treatment-induced apoptotic cell death. In conclusion, berberine-PDT could be used as a chemo-sensitizer by promoting cell death through activation of a ROS/p38/Caspase cascade.

Keywords

Berberine; Cisplatin; Melanoma cancer; Photodynamic therapy (PDT); ROS.

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