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Inhibition of Hepatocellular Carcinoma Growth by Ethyl Acetate Extracts of Apulian Brassica oleracea L. and Crithmum maritimum L.

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Abstract

Nowadays, a growing body of evidence supports the view that plants offer an extraordinary opportunity to discover and develop new promising therapeutic strategies for many diseases, including cancer. Here we tested the anticancer action against Hepatocellular carcinoma (HCC) of extracts obtained from two plants harvested in Apulia, namely Brassica oleracea L. and Crithmum maritimum L. B. oleracea was grown in biodynamical agriculture without any agrochemical input, instead C. maritimum was collected on Apulian coasts and is still commonly eaten in Apulia. HCC, one of the most frequent tumors worldwide, is estimated to become the third leading cause of cancer-related deaths in Western Countries by 2030. The approved synthetic drugs for the treatment of HCC are currently inadequate in terms of therapeutic results and tolerability. Hence, aim of the present study was to test the anticancer action against HCC of extracts obtained from Brassica oleracea L. and Crithmum maritimum L. We preliminary prepared extracts from both plants using four solvents with different polarity: hexane, ethyl acetate, methanol and ethanol. Then, we tested the effect of the different fractions in inhibiting HCC cell growth. Finally, we characterized the mechanism of action of the most effective fraction. We found that ethyl acetate fractions from both plants were the most effective in inhibiting HCC growth. In particular, we demonstrated that these fractions effectively reduce HCC growth by exerting, on one hand, a cytostatic effect through their action on the cell cycle, and on the other hand by triggering apoptosis and necrosis. Our findings support the notion that ethyl acetate fractions from Apulian B. oleracea and C. maritimum can be in perspective considered as promising tools to expand the opportunities to identify new and not toxic anticancer therapeutic approaches for HCC. Further pharmacological investigations will shed light on how this could be effectively achieved.

Experimental workflow for the detection of the ethyl acetate extract of Brassica oleracea L. and Crithmum maritimum L. as an active fraction in inhibiting HCC cell growth

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Abbreviations

ANOVA:

one-way analysis of variance

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

dimethyl sulfoxide

EtOH:

ethanol

FBS:

fetal bovine serum

HCC:

hepatocellular carcinoma

HPLC:

high performance liquid chromatography

MetS:

metabolic syndrome

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NAFLD:

non-alcoholic fatty liver disease

PBS:

phosphate buffered saline

SRB:

sulforhodamine B

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Acknowledgements

We are grateful to Ms. Loredana Acquaro for her precious technical support and to Dr. Marco Troisi for his technical support with the high-performance liquid chromatographic analysis. We are also in debt with Mr. Vito Moretti, who kindly provided us with B. oleracea, which was harvested in his biodynamic agricultural farm “La Calamita Rosa” (Castellaneta, Taranto, Italy).

Funding

This work was supported by Agenzia Regionale Strategica per la Salute ed. il Sociale – ARESS Puglia – in accordance with the project “The Apulian Lifestyle” – Delibera di Giunta n. 556 (18/04/2017).

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Authors and Affiliations

  1. Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy

    Davide Gnocchi, Carlo Sabbà & Antonio Mazzocca

  2. Department of Organic Agriculture, CIHEAM - Mediterranean Agronomic Institute of Bari, 70010, Valenzano, BA, Italy

    Gianluigi Cesari, Generosa Jenny Calabrese & Roberto Capone

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  1. Davide Gnocchi
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  2. Gianluigi Cesari
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Correspondence to Antonio Mazzocca.

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Gnocchi, D., Cesari, G., Calabrese, G.J. et al. Inhibition of Hepatocellular Carcinoma Growth by Ethyl Acetate Extracts of Apulian Brassica oleracea L. and Crithmum maritimum L.. Plant Foods Hum Nutr 75, 33–40 (2020). https://doi.org/10.1007/s11130-019-00781-3

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