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Published on: January 19, 2024
Dioscin (saponin)-induced generation of reactive oxygen species through mitochondria dysfunction: a proteomic-based
Ying Wang1, Chi-Ming Che, Jen-Fu Chiu
1Department of Chemistry, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Abstract:
It is generally believed that traditional Chinese medicine such as saponins has great value as potent cancer prevention and chemotherapeutic agents; however, the molecular basis for their activities is for the most part lacking. In the present study, we used proteomics to examine the cytotoxic effect of dioscin, a glucoside saponin, on human myeloblast leukemia HL-60 cells. Dioscin induced apoptosis in HL-60 cells in a time-dependent manner. Protein profiling of the microsomal fraction with enriched plasma membrane proteins isolated from HL-60 cells revealed that proteins act as chaperones and/or mediators of protein folding and were substantially altered in expression cells upon dioscin stimuli. Further biochemical study indicated that mitochondria dysfunction caused generation of reactive oxygen species (ROS), leading to the changes in protein expression. The mitochondrial transmembrane potential (DeltaPsi m) inhibitor aristolochic acid (ArA) partially abrogated the dioscin-initiated death receptor apoptosis pathway and cell death. The current study provided detailed evidence to support that dioscin is capable of inducing apoptosis in mammalian cells, in which the mitochondria-initiated apoptosis pathway plays an important role.
Insights
Dioscin, a saponin from traditional Chinese medicine, induces programmed cell death (apoptosis) in leukemia cells. This study reveals mitochondria dysfunction and altered protein expression are key mechanisms in dioscin
Area of Science:
- Biochemistry
- Molecular Biology
- Traditional Chinese Medicine
Background:
- Saponins, including dioscin, are explored for anticancer potential.
- The molecular mechanisms underlying their cytotoxic effects remain largely unelucidated.
- Understanding these mechanisms is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the cytotoxic effects of dioscin on human myeloblast leukemia HL-60 cells.
- To elucidate the molecular pathways involved in dioscin-induced apoptosis.
- To explore the role of proteomics in understanding the action of traditional Chinese medicine compounds.
Main Methods:
- Proteomics analysis of HL-60 cells treated with dioscin.
- Isolation and analysis of microsomal and plasma membrane proteins.
- Biochemical assays to assess mitochondrial function and reactive oxygen species (ROS) generation.
- Investigation of the mitochondrial transmembrane potential (ΔΨm) and apoptosis pathways.
Main Results:
- Dioscin induced time-dependent apoptosis in HL-60 cells.
- Proteomic analysis revealed significant alterations in chaperone and protein folding mediator expression.
- Mitochondrial dysfunction and subsequent ROS generation were observed.
- Aristolochic acid partially inhibited dioscin-induced apoptosis, implicating mitochondria.
Conclusions:
- Dioscin effectively induces apoptosis in leukemia cells.
- Mitochondria-initiated apoptosis pathways are critical to dioscin's cytotoxic action.
- This study provides molecular evidence for dioscin's potential as an anticancer agent.
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