Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization

<i>Azorella glabra</i> Wedd. (AG) is traditionally used to treat gonorrhea or kidney’s problems. The antioxidant, antidiabetic, anticholinesterase and in vitro antitumor activities of AG extracts were recently reported. The aim of this work was to investigate anti-leukemic properties of...

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Main Authors: Daniela Lamorte, Immacolata Faraone, Ilaria Laurenzana, Stefania Trino, Daniela Russo, Dilip K. Rai, Maria Francesca Armentano, Pellegrino Musto, Alessandro Sgambato, Luciana De Luca, Luigi Milella, Antonella Caivano
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/25/21/4890
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author Daniela Lamorte
Immacolata Faraone
Ilaria Laurenzana
Stefania Trino
Daniela Russo
Dilip K. Rai
Maria Francesca Armentano
Pellegrino Musto
Alessandro Sgambato
Luciana De Luca
Luigi Milella
Antonella Caivano
author_facet Daniela Lamorte
Immacolata Faraone
Ilaria Laurenzana
Stefania Trino
Daniela Russo
Dilip K. Rai
Maria Francesca Armentano
Pellegrino Musto
Alessandro Sgambato
Luciana De Luca
Luigi Milella
Antonella Caivano
author_sort Daniela Lamorte
collection DOAJ
description <i>Azorella glabra</i> Wedd. (AG) is traditionally used to treat gonorrhea or kidney’s problems. The antioxidant, antidiabetic, anticholinesterase and in vitro antitumor activities of AG extracts were recently reported. The aim of this work was to investigate anti-leukemic properties of AG chloroform fraction (AG CHCl<sub>3</sub>) and of its ten sub-fractions (I-X) and to identify their possible bioactive compounds. We determined their in vitro antioxidant activity using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO) and superoxide anion (SO) assays, and their phytochemical profile by spectrophotometric and LC-MS/MS techniques. I-X action on two acute myeloid leukemia (AML) cell lines viability, apoptosis and cell cycle were evaluated by MTS, western blotting and cytofluorimetric assays. Different polyphenol, flavonoid and terpenoid amount, and antioxidant activity were found among all samples. Most of I-X induced a dose/time dependent reduction of cell viability higher than parent extract. IV and VI sub-fractions showed highest cytotoxic activity and, of note, a negligible reduction of healthy cell viability. They activated intrinsic apoptotic pathway, induced a G<sub>0</sub>/G<sub>1</sub> block in leukemic cells and, interestingly, led to apoptosis in patient AML cells. These activities could be due to mulinic acid or azorellane terpenoids and their derivatives, tentatively identified in both IV and VI. In conclusion, our data suggest AG plant as a source of potential anti-AML agents.
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spelling doaj.art-bc4fce272e444d40895d54828289b19c2023-11-20T18:10:11ZengMDPI AGMolecules1420-30492020-10-012521489010.3390/molecules25214890Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound CharacterizationDaniela Lamorte0Immacolata Faraone1Ilaria Laurenzana2Stefania Trino3Daniela Russo4Dilip K. Rai5Maria Francesca Armentano6Pellegrino Musto7Alessandro Sgambato8Luciana De Luca9Luigi Milella10Antonella Caivano11Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, ItalyDepartment of Science, University of Basilicata, V.le dell’Ateneo Lucano 10, 85028 Rionero in Vulture, Potenza, ItalyLaboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, ItalyLaboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, ItalyDepartment of Science, University of Basilicata, V.le dell’Ateneo Lucano 10, 85028 Rionero in Vulture, Potenza, ItalyDepartment of Food BioSciences, Teagasc Food Research Centre Ashtown, D15KN3K Dublin, IrelandDepartment of Science, University of Basilicata, V.le dell’Ateneo Lucano 10, 85028 Rionero in Vulture, Potenza, ItalyHematology and Stem Cell Transplantation Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, ItalyScientific Direction, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, ItalyUnit of Clinical Pathology, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, ItalyDepartment of Science, University of Basilicata, V.le dell’Ateneo Lucano 10, 85028 Rionero in Vulture, Potenza, ItalyUnit of Clinical Pathology, Centro di Riferimento Oncologico della Basilicata (IRCCS CROB), 85028 Rionero in Vulture, Potenza, Italy<i>Azorella glabra</i> Wedd. (AG) is traditionally used to treat gonorrhea or kidney’s problems. The antioxidant, antidiabetic, anticholinesterase and in vitro antitumor activities of AG extracts were recently reported. The aim of this work was to investigate anti-leukemic properties of AG chloroform fraction (AG CHCl<sub>3</sub>) and of its ten sub-fractions (I-X) and to identify their possible bioactive compounds. We determined their in vitro antioxidant activity using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO) and superoxide anion (SO) assays, and their phytochemical profile by spectrophotometric and LC-MS/MS techniques. I-X action on two acute myeloid leukemia (AML) cell lines viability, apoptosis and cell cycle were evaluated by MTS, western blotting and cytofluorimetric assays. Different polyphenol, flavonoid and terpenoid amount, and antioxidant activity were found among all samples. Most of I-X induced a dose/time dependent reduction of cell viability higher than parent extract. IV and VI sub-fractions showed highest cytotoxic activity and, of note, a negligible reduction of healthy cell viability. They activated intrinsic apoptotic pathway, induced a G<sub>0</sub>/G<sub>1</sub> block in leukemic cells and, interestingly, led to apoptosis in patient AML cells. These activities could be due to mulinic acid or azorellane terpenoids and their derivatives, tentatively identified in both IV and VI. In conclusion, our data suggest AG plant as a source of potential anti-AML agents.https://www.mdpi.com/1420-3049/25/21/4890<i>Azorella glabra</i> Wedd.<i>Azorella diapensioides</i> A. Gray<i>yareta</i>phytochemicalsterpenoidsantioxidant
spellingShingle Daniela Lamorte
Immacolata Faraone
Ilaria Laurenzana
Stefania Trino
Daniela Russo
Dilip K. Rai
Maria Francesca Armentano
Pellegrino Musto
Alessandro Sgambato
Luciana De Luca
Luigi Milella
Antonella Caivano
Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization
Molecules
<i>Azorella glabra</i> Wedd.
<i>Azorella diapensioides</i> A. Gray
<i>yareta</i>
phytochemicals
terpenoids
antioxidant
title Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization
title_full Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization
title_fullStr Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization
title_full_unstemmed Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization
title_short Advances in <i>Azorella glabra</i> Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization
title_sort advances in i azorella glabra i wedd extract research in vitro antioxidant activity antiproliferative effects on acute myeloid leukemia cells and bioactive compound characterization
topic <i>Azorella glabra</i> Wedd.
<i>Azorella diapensioides</i> A. Gray
<i>yareta</i>
phytochemicals
terpenoids
antioxidant
url https://www.mdpi.com/1420-3049/25/21/4890
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