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Published on: January 22, 2019
The effect of quercetin and imperatorin on programmed cell death induction in T98G cells in vitro
Dorota Bądziul1, Joanna Jakubowicz-Gil1, Ewa Langner2
1Department of Comparative Anatomy and Anthropology, Institute of Biology, Maria Curie-Sklodowska University, Lublin, Poland.
Background:
High expression of HSP27 and HSP72 in glioma cells has been closely associated with chemoresistance and decreased sensitivity to programmed cell death induction. Therefore, it is important to devise therapies that effectively target invasive cancer cells by inducing cell death. The aim of our study was to assess the effect of quercetin and imperatorin applied separately and in combinations on the apoptosis and autophagy induction in human T98G cells cultured in vitro.
Methods:
Cell death induction was analyzed by the staining method. The Western blotting technique and fluorimetric measurements of activity were used to assess the expression of marker proteins of apoptosis and autophagy. The specific siRNA transfected method was used for blocking of the expression of HSP27 and HSP72 genes.
Results:
The experiments revealed the highest percentage of apoptotic cells after using a 50?M concentration of both compounds. Simultaneous quercetin and imperatorin administration induced apoptosis more effectively than incubation with single drugs. These results were accompanied with decreased HSP27 and HSP72 expression, and a high level of caspase-3 and caspase-9 activity. Autophagy was not observed. Additional experiments were performed on a cell line with blocked Hsp27 and Hsp72 expression and significant increase the sensitivity to apoptosis induction upon quercetin and imperatorin treatment was noticed.
Conclusions:
The present study indicates that quercetin and imperatorin are potent apoptosis inducers, especially when they act synergistically, which may be a promising combination useful in glioma therapy. Our results also demonstrated that blocking the HSP27 and HSP72 gene expression might serve as a therapeutic target for the human brain cancer.
Insights
Quercetin and imperatorin synergistically induce apoptosis in T98G glioma cells, offering a promising therapeutic strategy. Blocking heat shock proteins HSP27 and HSP72 enhances this cell death induction.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- High expression of heat shock proteins (HSP27 and HSP72) in glioma cells correlates with chemoresistance and reduced apoptosis.
- Targeting invasive cancer cells through induced cell death is crucial for effective glioma therapy.
Purpose of the Study:
- To evaluate the effects of quercetin and imperatorin, alone and in combination, on apoptosis and autophagy induction in human T98G glioma cells.
- To investigate the role of HSP27 and HSP72 in mediating the cellular response to these compounds.
Main Methods:
- Cell death induction assessed via staining methods.
- Apoptosis and autophagy marker protein expression analyzed by Western blotting and fluorimetric assays.
- HSP27 and HSP72 gene expression blocked using siRNA transfection.
Main Results:
- Quercetin and imperatorin combination treatment at 50µM significantly increased apoptosis compared to single-drug application.
- This synergistic effect was associated with decreased HSP27/HSP72 expression and elevated caspase-3/caspase-9 activity.
- Autophagy was not induced; however, blocking HSP27/HSP72 expression enhanced sensitivity to quercetin and imperatorin-induced apoptosis.
Conclusions:
- Quercetin and imperatorin act as potent apoptosis inducers, particularly in combination, presenting a promising therapeutic approach for glioma.
- Inhibition of HSP27 and HSP72 gene expression represents a potential therapeutic target for human brain cancers.
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