<i>Pinus mugo</i> Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

Muhammed Ashiq Thalappil; Elena Butturini; Alessandra Carcereri de Prati; Ilaria Bettin; Lorenzo Antonini; Filippo Umberto Sapienza; Stefania Garzoli; Rino Ragno; Sofia Mariotto

doi:10.3390/molecules27154834

Molecules (Jul 2022)

<i>Pinus mugo</i> Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

Muhammed Ashiq Thalappil,
Elena Butturini,
Alessandra Carcereri de Prati,
Ilaria Bettin,
Lorenzo Antonini,
Filippo Umberto Sapienza,
Stefania Garzoli,
Rino Ragno,
Sofia Mariotto

Affiliations

Muhammed Ashiq Thalappil: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, 37134 Verona, Italy
Elena Butturini: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, 37134 Verona, Italy
Alessandra Carcereri de Prati: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, 37134 Verona, Italy
Ilaria Bettin: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, 37134 Verona, Italy
Lorenzo Antonini: Department of Drug Chemistry and Technology, Rome Center for Molecular Design, Sapienza University of Rome, 00185 Rome, Italy
Filippo Umberto Sapienza: Department of Drug Chemistry and Technology, Rome Center for Molecular Design, Sapienza University of Rome, 00185 Rome, Italy
Stefania Garzoli: Department of Drug Chemistry and Technology, Sapienza University of Rome, 00185 Rome, Italy
Rino Ragno: Department of Drug Chemistry and Technology, Rome Center for Molecular Design, Sapienza University of Rome, 00185 Rome, Italy
Sofia Mariotto: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, 37134 Verona, Italy

DOI: https://doi.org/10.3390/molecules27154834
Journal volume & issue: Vol. 27, no. 15
p. 4834

Abstract

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Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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