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Published on: June 9, 2023
Galangin potentiates human breast cancer to apoptosis induced by TRAIL through activating AMPK
Wei Song1, Chong-Yang Yan2, Qian-Qian Zhou3
1Huai'an First People's Hospital, Nanjing Medical University,No.6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu, 223001, China.
Abstract:
Breast cancer is reported as the most frequent tumor with limited treatments among the female worldwide. Galangin, a natural active compound 3, 5, 7-trihydroxyflavone, is a type of bioflavonoid isolated from the Alpinia galangal root and suggested to induce apoptosis in various cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective anti-tumor agent for human breast cancer. Promoted expression of CHOP, a down-streaming transcription factor for endoplasmic reticulum stress (ER stress), enhanced death factor 4 (DR4) activity and accelerated reactive oxygen species (ROS) as well as cell death. Adenosine monophosphate-activated protein kinase (AMPK) is crucial for various cancers mortality. In the present study, galangin regulated ER stress to augment CHOP and DR4 expression levels, sensitizing TRAIL activity, leading to human breast cancer cell apoptosis through Caspase-3 activation, which was associated with AMPK phosphorylation. In addition, AMPK inhibition and silence reduced anti-cancer activity of galangin and TRAIL in combinational treatment. Hence, our study indicated that galangin could effectively stimulate human breast cancer cells to TRAIL-induced apoptosis through TRAIL/Caspase-3/AMPK signaling pathway. AMPK signaling pathway activation by galangin might be of benefit for promoting the effects of TRAIL-regulated anti-tumor therapeutic strategy.
Insights
Galangin enhances TRAIL-induced apoptosis in breast cancer by activating the AMPK signaling pathway. This natural compound sensitizes cancer cells to TRAIL, promoting cell death via Caspase-3 activation.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Breast cancer is a leading cause of cancer death in women, with limited treatment options.
- Galangin, a natural flavonoid, shows potential anti-cancer properties.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent for breast cancer.
Purpose of the Study:
- To investigate the mechanism by which galangin enhances TRAIL-induced apoptosis in human breast cancer cells.
- To explore the role of endoplasmic reticulum (ER) stress and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in galangin's anti-cancer effects.
Main Methods:
- Human breast cancer cell lines were treated with galangin and/or TRAIL.
- Expression levels of CHOP, DR4, and activated Caspase-3 were analyzed.
- AMPK phosphorylation was assessed.
- The effects of AMPK inhibition and silencing on cell apoptosis were evaluated.
Main Results:
- Galangin upregulated CHOP and DR4 expression, sensitizing cells to TRAIL-induced apoptosis.
- Galangin-induced apoptosis was mediated by Caspase-3 activation and associated with AMPK phosphorylation.
- Inhibition or silencing of AMPK diminished the combined anti-cancer effects of galangin and TRAIL.
Conclusions:
- Galangin effectively promotes TRAIL-induced apoptosis in human breast cancer cells via the TRAIL/Caspase-3/AMPK signaling pathway.
- Activating the AMPK pathway with galangin may enhance TRAIL-based anti-cancer therapeutic strategies.
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