Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells

Katerina Gioti; Anastasia Papachristodoulou; Dimitra Benaki; Sophia Havaki; Apostolos Beloukas; Argyro Vontzalidou; Nektarios Aligiannis; Alexios-Leandros Skaltsounis; Emmanuel Mikros; Roxane Tenta

doi:10.1055/a-0954-6704

Planta Medica, Inhaltsverzeichnis

Planta Med 2019; 85(11/12): 997-1007
DOI: 10.1055/a-0954-6704

Biological and Pharmacological Activities

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells^{[
¹
]}

Katerina Gioti

¹Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Kallithea, Greece

,

Anastasia Papachristodoulou

¹Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Kallithea, Greece

²Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Zografou, Greece

,

Dimitra Benaki

²Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Zografou, Greece

,

Sophia Havaki

³Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

,

Apostolos Beloukas

⁴Department of Biomedical Sciences, School of Health Sciences, University of West Attica, Greece

⁵Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom

,

Argyro Vontzalidou

⁶Faculty of Pharmacy, Department of Pharmacognosy and Natural Products Chemistry, University of Athens, Zografou, Greece

,

Nektarios Aligiannis

⁶Faculty of Pharmacy, Department of Pharmacognosy and Natural Products Chemistry, University of Athens, Zografou, Greece

,

Alexios-Leandros Skaltsounis

⁶Faculty of Pharmacy, Department of Pharmacognosy and Natural Products Chemistry, University of Athens, Zografou, Greece

,

Emmanuel Mikros

²Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Zografou, Greece

,

Roxane Tenta

¹Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Kallithea, Greece

› Institutsangaben

Abstract

Silymarin-enriched extract (SEE) is obtained from Silybum marianum (Asteraceae). Doxorubicin (DXR) is a widely used chemotherapeutical yet with severe side effects. The goal of the present study was to assess the pharmacologic effect of SEE and its bioactive components silibinin and silychristine when administrated alone or in combination with DXR in the human prostate cancer cells (PC-3). PC-3 cells were treated with SEE, silibinin (silybins A and B), silychristine, alone, and in combination with DXR, and cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis, and autophagy rate were assessed by flow cytometry. Expression levels of autophagy-related genes were quantified by qRT-PCR, ELISA and western blot while transmission electron microscopy was performed to reveal autophagic structures. Finally, NMR spectrometry was used to identify specific metabolites related to autophagy. SEE inhibited PC-3 cell proliferation in a dose-dependent manner while the co-treatment (DXR-SEE) revealed an additive cytotoxic effect. Cell cycle, apoptosis, and autophagy variations were observed in addition to altered expression levels of autophagy related genes (LC3, p62, NBR1, Beclin1, ULK1, AMBRA1), while several modifications in autophagic structures were identified after DXR-SEE co-treatment. Furthermore, treated cells showed a different metabolic profile, with significant alterations in autophagy-related metabolites such as branched-chain amino acids. In conclusion, the DXR-SEE co-treatment provokes perturbations in the autophagic mechanism of prostate cancer cells (PC-3) compared to DXR treatment alone, causing an excessive cell death. These findings propose the putative use of SEE as an adjuvant cytotoxic agent.

Key words

Silybum marianum - Asteraceae - silymarin - doxorubicin - prostate cancer - autophagy

Volltext

Referenzen

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Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells[ 1 ]

Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells^{[
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]}