TY - JOUR
T1 - Advances in Azorella glabra Wedd. Extract research
T2 - In vitro antioxidant activity, antiproliferative effects on acute myeloid leukemia cells and bioactive compound characterization
AU - Lamorte, Daniela
AU - Faraone, Immacolata
AU - Laurenzana, Ilaria
AU - Trino, Stefania
AU - Russo, Daniela
AU - Rai, Dilip K.
AU - Armentano, Maria Francesca
AU - Musto, Pellegrino
AU - Sgambato, Alessandro
AU - de Luca, Luciana
AU - Milella, Luigi
AU - Caivano, Antonella
N1 - Funding Information:
Funding: This research was funded by Italian Minister of Health–Ricerca corrente 2019. This work was supported by the Regione Basilicata; Project ALIMINTEGRA, GO NUTRIBAS financed on 16.1 PSR Basilicata founding ex D.G.R. n◦ 312/17 CUP: C31G18000210002.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/22
Y1 - 2020/10/22
N2 - Azorella glabra 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 CHCl3) 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 G0/G1 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.
AB - Azorella glabra 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 CHCl3) 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 G0/G1 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.
KW - Acute myeloid leukemia
KW - Antioxidant
KW - Apoptosis
KW - Azorella diapensioides A. Gray
KW - Azorella glabra Wedd
KW - Cell cycle arrest
KW - Cytotoxic effect
KW - KG1
KW - MV4-11
KW - Phytochemicals
KW - Terpenoids
KW - Yareta
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U2 - 10.3390/molecules25214890
DO - 10.3390/molecules25214890
M3 - Article
C2 - 33105817
AN - SCOPUS:85094856220
VL - 25
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 21
M1 - 4890
ER -