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 ones 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. A009 in vitro was additive to cisplatin and 5-FU to reduce cancer cell growth, while it did not further reduced growth of rat cardiomyocytes treated with cisplatin and 5-FU. A009 cardioprotective effects towards 5-FU chemotherapy were further investigated in vitro, using cardiomyocytes freshly isolated from mice pups. A009 mitigated toxicity of the fluoropyrimidine. Our study demonstrates that the polyphenol rich purified A009 extracts enhances 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.
Chemical and biological properties of a sandy loam soil amended with olive mill waste, solid or liquid form, in vitro
