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 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.
Highlights
Flavones are polyphenolic compounds of the flavonoid class
We describe for the first time the enhancement of rhsTRAIL-mediated apoptosis in cancer ceInllsoubrywnoinrke, flwaevdoensecsri:b5e-fHorF,th6e-HfirFs,t7t-iHmFe tahnedentheainrcnemewenstyonf trhhesTtiRcAdIeLr-imvaetdiviaetsedwaipthopatnosaisceintyl or a buctaynrcyelrgcreolluspb.y nine flavones: 5-HF, 6-HF, 7-HF and their new synthetic derivatives with an acetyl or a butyryl group
It has been proven that 6-HF exhibited a growth inhibitory effect in SF295 glioma cells, HCT15 and HCT15CLO2 colon cancer cells, whereas 7-HF did not exert any cytotoxicity against these cell lines [27]
Summary
Flavones are polyphenolic compounds of the flavonoid class. Natural or synthetic flavones possess antioxidant, antimicrobial, anti-inflammatory, chemopreventive and/or anticancer properties and have beneficial effects on health [1,2,3,4,5].Because biochemical action depends on the individual flavonoid structure, each compound should be evaluated systematically to assess its individual biological potency. Flavones are polyphenolic compounds of the flavonoid class. Natural or synthetic flavones possess antioxidant, antimicrobial, anti-inflammatory, chemopreventive and/or anticancer properties and have beneficial effects on health [1,2,3,4,5]. Because biochemical action depends on the individual flavonoid structure, each compound should be evaluated systematically to assess its individual biological potency. The anticancer effects of flavone analogs alone and in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were analyzed. Flavones exhibit chemopreventive and antitumor actions by interfering with apoptosis or proliferation signaling and regulating the immune system [1,7,8]. TRAIL, a TNF (tumor necrosis factor) superfamily member, is considered to be an
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