Bronikowska Joanna, Szliszka Ewelina, Kostrzewa-Susłow Edyta, Jaworska Dagmara, Czuba Zenon P, Bednarski Piotr, Król Wojciech
Department 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.
Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, Wrocław 50375, Poland.
Int J Mol Sci. 2017 Jun 6;18(6):1211. doi: 10.3390/ijms18061211.
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.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）被确定为肿瘤细胞凋亡的强力激活剂，也是癌症治疗中最有前景的候选药物之一，对正常组织无毒性。然而，许多肿瘤细胞对TRAIL诱导的凋亡具有抗性。本研究的目的是分析9种黄酮类化合物：5-羟基黄酮、6-羟基黄酮、7-羟基黄酮及其新合成衍生物5-乙酰氧基黄酮、5-丁酰氧基黄酮、6-乙酰氧基黄酮、6-丁酰氧基黄酮、7-乙酰氧基黄酮和7-丁酰氧基黄酮对重组人可溶性TRAIL（rhsTRAIL）抗癌效果的改善作用。我们使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐试验、乳酸脱氢酶测定和膜联蛋白V-异硫氰酸荧光素染色，研究了新型结构相关黄酮增强rhsTRAIL对SW480和SW620结肠癌细胞的细胞毒性和凋亡作用。我们观察到黄酮类化合物的活性存在细微差异，这取决于它们的化学结构。我们的研究表明，所有9种黄酮均能显著增强rhsTRAIL诱导的细胞死亡（细胞毒性范围为36.8±1.7%-91.4±1.7%；凋亡增加33.0±0.7%-78.5±0.9%）。我们的研究证明了所测试的黄酮类化合物在基于TRAIL的抗癌治疗和预防中的潜在应用。
