Taraxacum mongolicum extract induced endoplasmic reticulum stress associated-apoptosis in triple-negative breast cancer cells
Xiao-Hong Li1, Xi-Ran He1, Yan-Yan Zhou2
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital and Institute, Beijing 100142, PR China.
Background:
Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied.
Aim Of The Study:
This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line.
Methodology:
Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract.
Results:
Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis.
Conclusion:
ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to treat TNBC.
Insights
Dandelion extract shows anti-cancer effects against triple-negative breast cancer (TNBC) by inducing cell death through endoplasmic reticulum (ER) stress. This natural compound may offer a new therapeutic strategy for TNBC treatment.
Area of Science:
- Phytochemistry
- Molecular Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Taraxacum mongolicum (dandelion) possesses known anti-cancer properties, but its mechanisms in TNBC require elucidation.
- Traditional use of dandelion for mammary conditions suggests potential efficacy.
Purpose of the Study:
- To investigate the therapeutic effects of dandelion extract on TNBC cells.
- To elucidate the molecular mechanisms underlying dandelion's anti-cancer activity in TNBC.
- To assess the role of endoplasmic reticulum (ER) stress in dandelion-induced apoptosis.
Main Methods:
- Preparation and chemical characterization of dandelion extract.
- Assessment of cell viability (MTT assay), cell cycle, and apoptosis (flow cytometry) in TNBC cells.
- Analysis of gene and protein expression (RT-PCR, Western blotting) and manipulation of ER stress pathways (caspase inhibitor, CHOP siRNA).
Main Results:
- Dandelion extract reduced MDA-MB-231 cell viability and induced G2/M phase arrest and apoptosis.
- Dandelion treatment increased cleaved caspase-3 and PARP, indicating apoptosis activation.
- ER stress pathways (PERK/eIF2α/ATF4/CHOP axis) were significantly activated, mediating apoptosis.
Conclusions:
- Dandelion extract exhibits anti-cancer effects in TNBC cells primarily through ER stress-induced apoptosis.
- The findings support dandelion extract as a potential complementary therapeutic agent for TNBC.
- Further research into dandelion's mechanisms could lead to novel TNBC treatment strategies.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:15Drugs that Stabilize Microtubules