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  2. Andrographolide elevates tumor necrosis factor-related apoptosis-inducing ligand lethality through reactive oxygen species accumulation and gasdermin E cleavage in breast cancer cells

Andrographolide elevates tumor necrosis factor-related apoptosis-inducing ligand lethality through reactive oxygen species accumulation and gasdermin E cleavage in breast cancer cells

  • Med Oncol. 2022 Nov 9;40(1):11. doi: 10.1007/s12032-022-01878-7.
Yueyuan Wang 1 Dan Huang 1 Tingting Song 1 Xiaoyan Qi 1 Mingxi Li 2 Hui Zhang 1 Yang Liu 1 Ming Yang 3
Affiliations

Affiliations

  • 1 Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, People's Republic of China.
  • 2 Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, People's Republic of China.
  • 3 Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, People's Republic of China. yangming@jlu.edu.cn.
Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is selectively lethal to Cancer cells and harmless to normal cells, making it a potential agent for Cancer therapy. However, some breast Cancer cells are resistant to TRAIL. This study revealed that andrographolide (Andro), an extract from Andrographis paniculate, a natural compound, sensitized breast Cancer cells to TRAIL-induced tumor suppression; it identified apoptosis-associated protein regulation, Reactive Oxygen Species accumulation, mitochondria membrane potential disruption, Caspase cascade activation, and gasdermin-E cleavage to be involved in the tumor lethality mediated by Andro combined with TRAIL treatment. The flow cytometry results showed the combination of Andro and TRAIL repressed breast Cancer cells by cell death induction, and the assessment of combined index indicated that the combined treatment with Andro and TRAIL repressed breast Cancer cells synergistically. Blotting results displayed Andro and TRAIL combination elevated TRAIL-associated receptors, death receptors 4 and 5, at protein levels. These results provided critical insight into breast Cancer patients' therapy and exploration direction for TRAIL clinical application.

Keywords

Andrographolide; Breast cancer; Gasdermin-E; Reactive oxygen species; TRAIL.

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