在肿瘤学研究中，人们正在大力寻找新方法来预防和治疗癌症这种危及生命的疾病。适应恶劣条件的特定植物物种可能具有可用于治疗癌症的独特特性。苦莓果实富含具有抗癌活性的次生代谢物，可能有助于癌症的预防和治疗。根据上述假设，主要目标我们研究的目的是评估饮食中给予 Aronia melanocarpa L. 果皮（0.3 和 3% [w/w] 两种浓度）在治疗性同基因 4T1 小鼠腺癌模型（化学诱导乳腺癌的化学预防模型）中的抗肿瘤作用在大鼠中进行细胞抗氧化测定，并使用 MCF-7 和 MDA-MB-231 癌细胞进行稳健的体外分析。测试的黑果果皮提取物中的主要代谢物是酚类衍生物，分为花青素和原花青素。在治疗模型中，野樱莓在较高和较低剂量下均显着缩小了 4T1 肿瘤的体积。在相同的肿瘤中，我们注意到与对照相比，有丝分裂活性指数出现显着的剂量依赖性下降。在化学预防模型中，两种剂量的野樱莓均显着增加了 Bax 的表达。此外，与对照组相比，野樱莓降低了 Bcl-2 和 VEGF 水平，增加了 Bax/Bcl-2 比率。与对照组和较低剂量的野樱莓组相比，当给予较高剂量的野樱莓时，caspase-3的细胞质表达显着增强。此外，与对照组相比，较高剂量的野樱莓表现出肿瘤干细胞标记物CD133的表达显着降低。此外，通过体内分析检查野樱莓对肿瘤组织的表观遗传影响，揭示了组蛋白化学修饰（特别是 H3K4m3 和 H3K9m3）、miRNA 表达（miR155、miR210 和 miR34a）以及抑癌基因（PTEN）甲基化状态的显着变化。和 TIMP3)。利用黑果果木甲醇提取物的体外研究表明，MCF-7 和 MDA-MB-231 细胞系具有显着的抗癌特性。在这方面进行了各种分析，包括刃天青、细胞周期、膜联蛋白 V/PI、caspase-3/7、Bcl-2、PARP 和线粒体膜电位。此外，野樱莓提取物增强了两种癌细胞系对表阿霉素的反应性。本研究首次在体内和体外分析了黑果野樱莓在选定的实验性乳腺癌模型中的抗肿瘤作用。野樱莓的抗肿瘤作用在临床实践中的利用仍然很少，需要精确和长期的临床评估。个体化的癌症类型分析和患者分层对于在临床肿瘤学的靶向抗癌策略中有效实施植物营养保健品至关重要。版权所有 © 2024 Dvorska, Mazurakova, Lackova, Sebova, Kajo, Samec, Brany, Svajdlenka, Treml, Mersakova, Strnadel, Adamkov、Lasabova、Biringer、Mojzis、Büsselberg、Smejkal、Kello 和 Kubatka。

Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer.Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment.Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells.The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines.This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.Copyright © 2024 Dvorska, Mazurakova, Lackova, Sebova, Kajo, Samec, Brany, Svajdlenka, Treml, Mersakova, Strnadel, Adamkov, Lasabova, Biringer, Mojzis, Büsselberg, Smejkal, Kello and Kubatka.