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首页> 外文期刊>The Journal of toxicological sciences >Promoting effects of carminic acid-enriched cochineal extracts on capsular invasive thyroid carcinomas through targeting activation of angiogenesis in rats.
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Promoting effects of carminic acid-enriched cochineal extracts on capsular invasive thyroid carcinomas through targeting activation of angiogenesis in rats.

机译:通过靶向激活大鼠血管生成,富含胭脂氨酸酸的胭脂树提取物对荚膜浸润性甲状腺癌的促进作用。

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摘要

Cochineal extracts (CE) is a coccid-derived natural food colorant containing carminic acid (CA) as an active ingredient that potentiates inhibition of tissue proteolysis mediated by activation of plasma hyaluronan-binding protein (PHBP). In our previous study, dietary administered CE (CA: 28.5% in CE) has shown to promote the macroscopic development of capsular invasive carcinomas (CICs) associated with up-regulation of angiogenesis-related genes in an intracapsular invasion model of experimental thyroid cancers using rats. However, the promoting effect of CE could not be confirmed histopathologically. The purpose of the present study was to confirm the promoting effect of CE through direct injections to animals on the development of CICs using this cancer invasion model. One week after initiation with N-bis(hydroxypropyl)nitrosamine, male F344/NSlc rats were administered CA-enriched CE (CA: 52.6% in CE) by intraperitoneal injections every other day (10 mg/kg body weight) during the promotion with 0.15% sulfadimethoxine in the drinking water for 8 weeks. The multiplicities of macroscopical CICs and the mean area of early capsular invasive foci estimated by Tenascin (TN)-C-immunoreactivity in the thyroid significantly increased with CE-treatment, while the number of TN-C-positive foci did not change with CE. Transcript level of Phbp and downstream genes unchanged; however, transcript level of angiogenesis-related genes, i.e, Vegfb and its transcription factor gene, Hif1a, those being downstream of phosphatase and tensin homolog (PTEN)/Akt signaling, up-regulated in the thyroid tissue with CE-administration. These results suggest that CE potentiates promotion activity by facilitating angiogenesis through activation of PTEN/Akt signaling without accompanying modification of PHBP-related proteolysis.
机译:胭脂树提取物(CE)是一种含有球蛋白的天然食用色素,其中含有胭脂红酸(CA)作为有效成分,可通过抑制血浆透明质酸结合蛋白(PHBP)的活化来增强对组织蛋白水解的抑制作用。在我们先前的研究中,饮食管理的CE(CA:28.5%的CE)已显示可促进与甲状腺癌的囊内浸润模型中血管生成相关基因上调相关的囊性浸润癌(CIC)的宏观发展。大鼠。然而,在组织病理学上不能证实CE的促进作用。本研究的目的是通过使用这种癌症侵袭模型来证实通过直接向动物注射CE对CICs发育的促进作用。在开始使用N-双(羟丙基)亚硝胺后的一周,雄性F344 / NSlc大鼠每隔一天腹膜内注射一次(10 mg / kg体重)富含CA的CE(CA:52.6%,在CE中)。饮用水中0.15%磺胺二甲氧嘧啶持续8周。经CE处理,甲状腺中的腱生蛋白(TN)-C-免疫反应性估计的宏观CIC的多样性和早期荚膜浸润灶的平均面积显着增加,而CE引起的TN-C阳性灶的数量没有变化。 Phbp和下游基因的转录水平保持不变;但是,与CE一起给药的甲状腺组织中,血管生成相关基因(即Vegfb及其转录因子基因Hif1a)的转录水平在磷酸酶和肌腱蛋白同源物(PTEN)/ Akt信号的下游。这些结果表明,CE通过激活PTEN / Akt信号传导促进血管生成而没有伴随PHBP相关蛋白水解的修饰而增强了促进活性。

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