Abstract 4044: An extract of olive oil wastewater enhances chemotherapy effects on breast cancer cells without exacerbating cardiovascular toxicity
Authors: Albini Adriana , Festa Marco M. , Baci Denisa , Benedetto Nadia , Gutmanska Karolina , Macrì Nicoletta , Finzi Giovanna , Sessa Fausto , Zacchigna Serena , Bruno Antonino , Noonan Douglas M. 
Published: June 2022

Abstract
Background: In cancer patients receiving chemotherapeutic agents, cardiovascular toxicities still remains one of the most undesirable side effects. One of the best known cardiotoxic agents is doxorubicin, a very powerful chemotherapeutic molecules for breast cancer. 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. A 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, on breast cancer cells when combined with chemotherapeutics, as well as its potential cardioprotective activities. We had previously reported additive effects with cisplatin in prostate cancer cells. In previous studies we have shown that 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. Here we used 5-fluorouracil as comparison.
Methods: Combination of A009 and chemotherapy was investigated in vitro on human breast cancer cell lines BT459, MDA-MB-234. The cardioprotective effects of the A009 extract were tested on H9C2 (cardiomyocytes) cells co-exposed to doxorubicin or 5-fluorouracil and in zebrafish embryos.
Results: Adding A009 to doxorubicin or 5-FU was effective in decreasing breast cancer cell growth in monolayer. Breast tumor spheroids morphologically appeared less stable and with reduced diameter when treated with A009 extracts and with the chemotherapeutic agents 5-FU or Doxo, additive effects were observed. A009 mitigated toxicity of doxorubicin or 5-FU on rat cardiomyocytes cells H9C2. Cardioprotective effects were observed by the combination of OMWW extracts with Doxorubicin in Zebrafish embryos. In human cardiomyocytes, we observed 5-FU induced upregulation of the proinflammatory IL6 mRNA, which was reduced by OMWW treatment.
Conclusions: Our study demonstrates that the polyphenol rich purified A009 extracts enhance the effect of chemotherapy of doxorubicin and 5-FU on breast cancer cells but mitigates chemotherapy adverse effects on heart in vivo and on cardiomyocytes, appearing as a potential cardio-oncological prevenzion agent.

Citation Format: Adriana Albini, Marco M. Festa, Denisa Baci, Nadia Benedetto, Karolina Gutmanska, Nicoletta Macrì, Giovanna Finzi, Fausto Sessa, Serena Zacchigna, Antonino Bruno, Douglas M. Noonan. An extract of olive oil wastewater enhances chemotherapy effects on breast cancer cells without exacerbating cardiovascular toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4044.