An Olive Oil Mill Wastewater Extract Improves Chemotherapeutic Activity Against Breast Cancer Cells While Protecting From Cardiotoxicity

Benedetto, Nadia; Calabrone, Luana; Gutmańska, Karolina; Macrì, Nicoletta; Cerrito, Maria Grazia; Ricotta, Riccardo; Pelosi, Giuseppe; Bruno, Antonino; Noonan, Douglas M.; Albini, Adriana

doi:10.3389/fcvm.2022.867867

Cited by 10 publications

(11 citation statements)

References 50 publications

(47 reference statements)

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“…Integra® Flowable Wound Matrix (FWM), was kindly provided and characterized by LifeSciences Corporation (Plainsboro, NJ, USA). The Cultrex Ultimatrix (Biotechne) (Minneapolis, MN, USA) at 10 mg/ml of concentration was used as matrix for in vivo angiogenesis matrix sponge assay [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis

et al. 2023

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Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy. Here, we compared the effectiveness of adipose mesenchymal stem cells (ASCs), use as cell suspension, ASC protein extract or ASC-conditioned-medium (i.e., soluble factors), combined with collagenic scaffold, in supporting in vivo angiogenesis. We also tested the capability of hypoxia in increasing the efficiency of ASC to promote angiogenesis, via soluble factors, both in vivo and in vitro. In vivo studies were performed using the Integra® Flowable Wound Matrix, and the Ultimatrix in sponge assay. Flow cytometry was used to characterize the scaffold- and sponge-infiltrating cells. Real-time PCR was used to evaluate the expression of pro-angiogenic factors by stimulating Human Umbilical-Vein Endothelial Cells with ASC-conditioned media, obtained in hypoxic and normoxic conditions. We found that, in vivo, ACS-conditioned media can support angiogenesis similar to ASCs and ASC protein extract. Also, we observed that hypoxia increases the pro-angiogenic activities of ASC-conditioned media, compared to normoxia, by generating a secretome enriched in pro-angiogenic soluble factors, with bFGF, Adiponectine, ENA78, GRO, GRO-a, and ICAM1-3, as most regulated factors. Finally, ASC-conditioned media, produced in hypoxic condition, induce the expression of pro-angiogenic molecules in HUVECs. Our results provide evidence that ASC-conditioned-medium can be proposed as a cell-free preparation able to support angiogenesis, thus providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

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Section: Methodsmentioning

confidence: 99%

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis

et al. 2023

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“…In a further study we investigated the anti-cancer effects of A009 on breast cancer cells (MDA-MB-231 and BT-549) when combined with chemotherapeutic agents such as doxorubicin, an anthracycline commonly used in breast cancer therapy, and 5-FU as the prototype fluoropyrimidine. In vitro experiments showed that A009 combined with doxorubicin or 5-FU effectively decreased breast cancer cell growth, and additive effects were observed in breast tumor spheroids ( 38 ). A009 was anti-angiogenic in the Matrigel sponge model containing breast cancer cells supernatants, and recruitment of T cells was increased by A009 ( 38 ).…”

Section: Review Methodologymentioning

confidence: 99%

“…In vitro experiments showed that A009 combined with doxorubicin or 5-FU effectively decreased breast cancer cell growth, and additive effects were observed in breast tumor spheroids ( 38 ). A009 was anti-angiogenic in the Matrigel sponge model containing breast cancer cells supernatants, and recruitment of T cells was increased by A009 ( 38 ).…”

Section: Review Methodologymentioning

confidence: 99%

From antiquity to contemporary times: how olive oil by-products and waste water can contribute to health

Albini,

Corradino

et al. 2023

Front. Nutr.

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Since antiquity, numerous advantages of olive oil and its by-products have been recognized in various domains, including cooking, skincare, and healthcare. Extra virgin olive oil is a crucial component of the Mediterranean diet; several of its compounds exert antioxidant, anti-proliferative, anti-angiogenic and pro-apoptotic effects against a variety of cancers, and also affect cellular metabolism, targeting cancer cells through their metabolic derangements. Numerous olive tree parts, including leaves, can contribute metabolites useful to human health. Olive mill waste water (OMWW), a dark and pungent liquid residue produced in vast amounts during olive oil extraction, contains high organic matter concentrations that may seriously contaminate the soil and surrounding waters if not managed properly. However, OMWW is a rich source of phytochemicals with various health benefits. In ancient Rome, the farmers would employ what was known as amurca, a mulch-like by-product of olive oil production, for many purposes and applications. Several studies have investigated anti-angiogenic and chemopreventive activities of OMWW extracts. The most prevalent polyphenol in OMWW extracts is hydroxytyrosol (HT). Verbascoside and oleuperin are also abundant. We assessed the impact of one such extract, A009, on endothelial cells (HUVEC) and cancer cells. A009 was anti-angiogenic in several in vitro assays (growth, migration, adhesion) and inhibited angiogenesis in vivo, outperforming HT alone. A009 inhibited cells from several tumors in vitro and in vivo and showed potential cardioprotective effects mitigating cardiotoxicity induced by chemotherapy drugs, commonly used in cancer treatment, and reducing up-regulation of pro-inflammatory markers in cardiomyocytes. Extracts from OMWW and other olive by-products have been evaluated for biological activities by various international research teams. The results obtained make them promising candidates for further development as nutraceutical and cosmeceutical agents or dietary supplement, especially in cancer prevention or even in co-treatments with anti-cancer drugs. Furthermore, their potential to offer cardioprotective benefits opens up avenues for application in the field of cardio-oncology.

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“…A009, a polyphenolrich Olive mill wastewater (OMWW) extract, was able to counteract the doxorubicin-induced cardiotoxic effects in the zebrafish eAIC model, which is consistent to its cardioprotective activities on rat and human cardiomyocytes. Intriguingly, this waste material from extra-virgin olive oil (EVOO) processing is able to increase the effects of breast cancer chemotherapy via its antiangiogenic and antiproliferative activities (60). While all of these aforementioned compounds are able to rescue cardiac dysfunction to a certain degree, therapeutic target genes for these compounds remain elusive and further mechanistic studies are needed to translate these discoveries to AIC patients.…”

Section: Utilization Of Eaic To Discover Therapeutic Strategiesmentioning

confidence: 99%

Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play

Moossavi

Lu²,

Herrmann³

et al. 2023

Front. Cardiovasc. Med.

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Anthracyclines are among the most potent chemotherapeutics; however, cardiotoxicity significantly restricts their use. Indeed, anthracycline-induced cardiotoxicity (AIC) fares among the worst types of cardiomyopathy, and may only slowly and partially respond to standard heart failure therapies including β-blockers and ACE inhibitors. No therapy specifically designed to treat anthracycline cardiomyopathy at present, and neither is it known if any such strategy could be developed. To address this gap and to elucidate the molecular basis of AIC with a therapeutic goal in mind, zebrafish has been introduced as an in vivo vertebrate model about a decade ago. Here, we first review our current understanding of the basic molecular and biochemical mechanisms of AIC, and then the contribution of zebrafish to the AIC field. We summarize the generation of embryonic zebrafish AIC models (eAIC) and their use for chemical screening and assessment of genetic modifiers, and then the generation of adult zebrafish AIC models (aAIC) and their use for discovering genetic modifiers via forward mutagenesis screening, deciphering spatial-temporal-specific mechanisms of modifier genes, and prioritizing therapeutic compounds via chemical genetic tools. Several therapeutic target genes and related therapies have emerged, including a retinoic acid (RA)-based therapy for the early phase of AIC and an autophagy-based therapy that, for the first time, is able to reverse cardiac dysfunction in the late phase of AIC. We conclude that zebrafish is becoming an important in vivo model that would accelerate both mechanistic studies and therapeutic development of AIC.

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An Olive Oil Mill Wastewater Extract Improves Chemotherapeutic Activity Against Breast Cancer Cells While Protecting From Cardiotoxicity

Cited by 10 publications

References 50 publications

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis

From antiquity to contemporary times: how olive oil by-products and waste water can contribute to health

Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play

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