A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity.
A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity.
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DOI：
10.3389/fphar.2021.694762
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发表时间：
2021
影响因子：
5.6
通讯作者：
Noonan DM
中科院分区：
文献类型：
--
作者：
Albini A;Festa MMG;Ring N;Baci D;Rehman M;Finzi G;Sessa F;Zacchigna S;Bruno A;Noonan DM
心血管毒性仍然是接受化疗的癌症患者最不利的副作用之一。特级初榨橄榄油(EVOO)富含抗癌多酚，具有抗炎、抗氧化活性，对心脏细胞具有保护作用。EVOO制剂的一个非常有趣的衍生品是富含多酚的橄榄磨废水(OMWW)的纯化提取物。在这里，我们研究了一种名为A009的OMWW制剂与化疗药物联合使用时的抗癌活性，以及它潜在的心脏保护活性。携带前列腺癌(PCA)异种移植瘤的小鼠接受顺铂单独或与A009联合治疗。在体内模型中，我们发现A009和顺铂在减轻前列腺癌肿瘤重量方面具有协同作用。对小鼠心脏进行分析，并用透射电子显微镜观察线粒体。与单独接受化疗的小鼠相比，A009提取物与顺铂联合治疗的小鼠心脏线粒体损伤减少，这表明了心脏保护作用。为了证实体内的结果，我们在体外用顺铂处理肿瘤细胞系和大鼠心肌细胞，分别加入和不加A009。另一种常用的化疗药物5-氟尿嘧啶(5-FU)也在本试验中进行了检测，观察到了类似的效果。在体外，A009与顺铂或5-FU联合应用能有效抑制前列腺癌和结肠癌细胞的生长，但不能进一步抑制顺铂或5-FU处理的大鼠心肌细胞的生长。用新鲜分离的小鼠心肌细胞进一步研究了A009对5-FU化疗所致副作用的心脏保护作用。A009可减轻5-FU对原代培养小鼠心肌细胞的毒性。我们的研究表明，富含多酚的纯化的A009提取物在体内外增强了化疗的效果，但减轻了化疗对心脏和分离的心肌细胞的不利影响。因此，橄榄磨坊废水提取物可能是癌症化疗患者心血管预防的潜在候选药物。
Cardiovascular toxicity remains one of the most adverse side effects in cancer patients receiving chemotherapy. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, anti-oxidant activities which could exert protective effects on heart cells. One very interesting derivative of EVOO preparation is represented by purified extracts from olive mill waste waters (OMWW) rich in polyphenols. Here, we have investigated the anti-cancer activity of a OMWW preparation, named A009, when combined with chemotherapeutics, as well as its potential cardioprotective activities. Mice bearing prostate cancer (PCa) xenografts were treated with cisplatin, alone or in combination with A009. In an in vivo model, we found synergisms of A009 and cisplatin in reduction of prostate cancer tumor weight. Hearts of mice were analyzed, and the mitochondria were studied by transmission electron microscopy. The hearts of mice co-treated with A009 extracts along with cisplatin had reduced mitochondria damage compared to the those treated with chemotherapy alone, indicating a cardioprotective role. To confirm the in vivo results, tumor cell lines and rat cardiomyocytes were treated with cisplatin in vitro, with and without A009. Another frequently used chemotherapeutic agent 5-fluorouracil (5-FU), was also tested in this assay, observing a similar effect. In vitro, the combination of A009 with cisplatin or 5-FU was effective in decreasing prostate and colon cancer cell growth, while it did not further reduce growth of rat cardiomyocytes also treated with cisplatin or 5-FU. A009 cardioprotective effects towards side effects caused by 5-FU chemotherapy were further investigated, using cardiomyocytes freshly isolated from mice pups. A009 mitigated toxicity of 5-FU on primary cultures of mouse cardiomyocytes. Our study demonstrates that the polyphenol rich purified A009 extracts enhance the effect of chemotherapy in vitro and in vivo, but mitigates chemotherpy adverse effects on heart and on isolated cardiomyocytes. Olive mill waste water extracts could therefore represent a potential candidate for cardiovascular prevention in patients undergoing cancer chemotherapy.
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影响因子：
5.6
作者：
El-Readi MZ;Al-Abd AM;Althubiti MA;Almaimani RA;Al-Amoodi HS;Ashour ML;Wink M;Eid SY
通讯作者：
Eid SY
影响因子：
--
作者：
Cheng YC;Sheen JM;Hu WL;Hung YC
通讯作者：
Hung YC
病理生理学，糖尿病心肌病的临床特征：天然多酚的治疗潜力。
影响因子：
5
作者：
Atale N;Yadav D;Rani V;Jin JO
通讯作者：
Jin JO
影响因子：
11.5
作者：
Albini, Adriana;Noonan, Douglas M.;Ferrari, Nicoletta
通讯作者：
Ferrari, Nicoletta
影响因子：
8.8
作者：
El-Abbassi, Abdelilah;Kiai, Hajar;Hafidi, Abdellatif
通讯作者：
Hafidi, Abdellatif