Abstract
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.
Highlights
Plant extracts play an important role in antitumor drug discovery thanks to their large structural diversity and low toxicity towards normal cells
Viability Analysis of acute myeloid leukemia (AML) Cells Treated with Azorella glabra (AG) CHCl3 Fraction
Most studies reported the extraction of bioactive compounds from aerial part of plants, including for that belonging to the Apiaceae family as Azorella glabra (AG) [2,8,9,10]
Summary
Plant extracts play an important role in antitumor drug discovery thanks to their large structural diversity and low toxicity towards normal cells. Of note, they can target different pathways, like proliferation and differentiation in malignant cells [1,2], but can reduce the resistance against chemotherapies [3,4] and can exhibit a synergistic effect with conventional drugs [5,6]. The selection and the polarity of solvents used for the extraction are crucial, as the nature of the extracted compounds depends on them. Due the high complexity of phytochemicals, the use of solvents having increasing polarity is useful for highly valued separations [11]
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