A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity

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.

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A polyphenol-rich extract of Olive Mill Wastewater Enhances cancer chemotherapy effects while mitigating cardiac toxicity.

10.1101/2021.04.08.438946 ◽

2021 ◽

Author(s):

Adriana Albini ◽

Marco M. G. Festa ◽

Nadja Ring ◽

Denisa Baci ◽

Michael Rehman ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Growth ◽

Tumor Cell ◽

Cell Lines ◽

Cancer Cell ◽

Heart Cells ◽

Cancer Cell Growth ◽

Rat Cardiomyocytes

Background. Cardiovascular toxicities still remain one of the most undesirable side effects in cancer patients receiving chemotherapy, and cardiotoxicity has been detected associated with many therapeutic regimens. A number of mechanisms are reported for these effects, some of which are related to inflammation, oxygen radical generation, mitochondrial damage. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, antioxidant activities which could exert protective effects on the heart cells. One very interesting derivative of EVOO preparation is represented by purified extract form waste waters. Here, we investigated the anti-cancer activity when combined with chemotherapeutics as well as potential cardioprotective activities of a polyphenol-rich extract from waste product of the EVOO, named A009. Methods and Results. Mice bearing prostate cancer (PCa) xenografts were treated with cisplatin with and without A009. Tumor cell growth was reduced by cis and by A009 and further hindered by the combination. The effects of the A009 extract on cardiovascular toxicities was investigated in vivo. The hearts of mice were analyzed, and the mitochondria were studied by transmission electron microscopy. A protection activity by A009 was observed. To confirm the in vivo data obtained with cisplatin therapy, tumor cell lines and rat cardiomyocytes were treated with cisplatin in vitro with and without A009. A009 enhanced cisplatin and 5FU reduced cancer cell growth while did not further affect co-treated rat cardiomyocytes. Another frequently used chemotherapeutic agent 5-fluorouracil (5FU), was also tested in this assay similar effects were observed. The cardioprotective effects of the A009 extract towards 5 FU chemotherapy were further investigated in a second system of in vitro cultures, on cardiomyocytes freshly isolated from mice pups. These cells were treated with 5-fluorouracil and A009. Wastewater extract mitigated the toxicity of the fluoropyrimidine. Conclusions. In vivo, we found synergisms of A009 and cisplatin in prostate cancer treatment. Hearts of mice xenografted with PCa cell lines and receiving co-treatment of A009 extracts along with cisplatin had reduced mitochondria damage compared to chemotherapy alone, indicating a cardioprotective role. A009 in vitro was additive to cisplatin and 5FU to reduce cancer cell growth while did not further affect rat cardiomyocytes cell cultures treated with cisplatin and 5FU. The A009 extract also rescued the proliferation rate of neonatal murine cardiomyocytes treated with 5-Fluorouracil. Our study demonstrates that the polyphenol-rich purified A009 extracts enhances the effect of chemotherapy in vitro and in vivo but mitigates effects on heart and heart cells. It could therefore represent a potential candidate for cardiovascular prevention in patients undergoing cancer chemotherapy.

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Effect of a Purified Extract of Olive Mill Waste water on Endothelial Cell Proliferation, Apoptosis, Migration and Capillary-Like Structure in vitro and in vivo

Journal of Bioanalysis & Biomedicine ◽

10.4172/1948-593x.s12-006 ◽

2015 ◽

Vol 01 (s12) ◽

Cited By ~ 1

Author(s):

Teresa Rossi Barbara Bassani

Keyword(s):

Waste Water ◽

Cell Proliferation ◽

Endothelial Cell ◽

Endothelial Cell Proliferation ◽

Olive Mill Waste ◽

Olive Mill Waste Water ◽

Mill Waste ◽

Olive Mill

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Mechanical stimulation of organogenic cardiomyocyte growth in vitro

AJP Cell Physiology ◽

10.1152/ajpcell.1996.270.5.c1284 ◽

1996 ◽

Vol 270 (5) ◽

pp. C1284-C1292 ◽

Cited By ~ 38

Author(s):

H. H. Vandenburgh ◽

R. Solerssi ◽

J. Shansky ◽

J. W. Adams ◽

S. A. Henderson

Keyword(s):

Mechanical Load ◽

Mechanical Stretch ◽

Neonatal Rat ◽

Cardiomyocyte Hypertrophy ◽

Heart Cells ◽

Mechanical Stimuli ◽

Rat Cardiomyocytes ◽

Morphological Alterations

Adherent cultures of neonatal rat cardiomyocytes were subjected to progressive, unidirectional lengthening for 2-4 days in serum-containing medium. This mechanical stretch (25% increase in initial length each day) simulates the eccentric mechanical load placed on in vivo heart cells by increases in postnatal blood pressure and volume. The in vitro mechanical stimuli initiated a number of morphological alterations in the confluent cardiomyocyte population which were similar to those occurring during in vivo heart growth. These include cardiomyocyte organization into parallel arrays of rod-shaped cells, increased cardiomyocyte binucleation, and cardiomyocyte hypertrophy by longitudinal cell growth. Stretch stimulated DNA synthesis in the noncardiomyocyte population but not in the cardiomyocytes. Myosin heavy chain (MHC) content increased 62% over 4 days of stretch and included increased accumulation of both fetal beta-MHC and adult alpha-MHC isoforms. This new model of stretch-induced cardiomyocyte hypertrophy may assist in examining some of the complex mechanogenic growth processes that occur in the rapidly enlarging neonatal heart.

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Regression of Castration-Resistant Prostate Cancer by a Novel Compound HG122

Frontiers in Oncology ◽

10.3389/fonc.2021.650919 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaonan Cong ◽

Yundong He ◽

Haigang Wu ◽

Dingxiang Wang ◽

Yongrui Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Target Genes ◽

Mrna Level ◽

Tumor Model ◽

Life Cycle Management ◽

Potential Candidate ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

Prostate cancer (PCa) is a common aggressive disease worldwide which usually progresses into incurable castration-resistant prostate cancer (CRPC) in most cases after 18–24 months treatment. Androgen receptor (AR) has been considered as a crucial factor involved in CRPC and the study of AR as a potential therapeutic target in CRPC may be helpful in disease control and life-cycle management. In this study, we identified a potent small molecule compound, HG122, that suppressed CRPC cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous and orthotopic tumor model. In addition, HG122 reduced the mRNA expression of PSA and TMPRSS2 which are target genes of AR, resulting in cell growth inhibition and metastasis suppression of CRPC, without affecting the expression of AR mRNA level. Mechanically, HG122 promoted AR protein degradation through the proteasome pathway impairing the AR signaling pathway. In conclusion, HG122 overcomes enzalutamide (ENZ) resistance in CRPC both in vitro and in vivo, thus suggesting HG122 is a potential candidate for the clinical prevention and treatment of CRPC.

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