Novel Structurally Related Flavones Augment Cell Death Induced by rhsTRAIL

Autor: Zenon P. Czuba, Ewelina Szliszka, Piotr Bednarski, Wojciech Król, Edyta Kostrzewa-Susłow, Dagmara Jaworska, Joanna Bronikowska
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: International Journal of Molecular Sciences; Volume 18; Issue 6; Pages: 1211
International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 18, Iss 6, p 1211 (2017)
ISSN: 1422-0067
DOI: 10.3390/ijms18061211
Popis: 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 the 3-(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.
Databáze: OpenAIRE