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Novel Structurally Related Flavones Augment Cell Death Induced by rhsTRAIL
Joanna Bronikowska1, Ewelina Szliszka2, Edyta Kostrzewa-Susłow3
1Department of Microbiology and Immunology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, Zabrze 41808, Poland. jbronikowska@sum.edu.pl.
Abstract:
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) was identified as a powerful activator of apoptosis in tumor cells and one of the most promising candidates for cancer therapy with no toxicity against normal tissues. However, many tumor cells are resistant to TRAIL-induced apoptosis. The aim of this work was to analyze the improvement of the anticancer effect of rhsTRAIL (recombinant human soluble TRAIL) by nine flavones: 5-Hydroxyflavone, 6-Hydroxyflavone, 7-Hydroxyflavone and their new synthetic derivatives 5-acetoxyflavone, 5-butyryloxyflavone, 6-acetoxyflavone, 6-butyryloxyflavone, 7-acetoxyflavone and 7-butyryloxyflavone. We examined the cytotoxic and apoptotic effects of rhsTRAIL enhanced by novel structurally-related flavones on SW480 and SW620 colon cancer cells using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, the lactate dehydrogenase assay and annexin V-FITC fluorescence staining. We observed a slight difference in the activities of the flavones that was dependent on their chemical structure. Our study indicates that all nine flavones significantly augment cell death by rhsTRAIL (cytotoxicity range 36.8 ± 1.7%-91.4 ± 1.7%; apoptosis increase of 33.0 ± 0.7%-78.5 ± 0.9%). Our study demonstrates the potential use of tested flavones in TRAIL-based anticancer therapy and prevention.
Insights
Nine novel flavones enhance the cancer-fighting power of recombinant human soluble TRAIL (rhsTRAIL). These compounds significantly increase rhsTRAIL-induced apoptosis and cytotoxicity in colon cancer cells, offering potential for improved cancer therapies.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic due to its selective apoptosis induction in tumor cells.
- Resistance to TRAIL-mediated apoptosis is a significant challenge in cancer treatment.
- Flavones are natural compounds with potential therapeutic properties.
Purpose of the Study:
- To investigate the potential of nine novel flavones to enhance the anticancer effects of recombinant human soluble TRAIL (rhsTRAIL).
- To evaluate the cytotoxic and apoptotic effects of rhsTRAIL combined with these flavones on colon cancer cells.
Main Methods:
- Utilized SW480 and SW620 colon cancer cell lines.
- Assessed cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) assay.
- Quantified apoptosis via annexin V-FITC fluorescence staining.
Main Results:
- All nine tested flavones significantly augmented rhsTRAIL-induced cell death.
- Cytotoxicity enhancement ranged from 36.8% to 91.4%.
- Apoptosis increase ranged from 33.0% to 78.5%, with minor variations based on flavone chemical structure.
Conclusions:
- The nine novel flavones effectively enhance the anticancer activity of rhsTRAIL against colon cancer cells.
- These flavones demonstrate potential as adjuncts in TRAIL-based cancer therapy.
- Further research into flavone-TRAIL combinations could lead to novel cancer prevention and treatment strategies.
