title: The Hexane Fraction of Bursera microphylla A Gray Induces p21-Mediated Antiproliferative and Proapoptotic Effects in Human Cancer-Derived Cell Lines.
abstract: Bursera microphylla (BM), one of the common elephant trees, is widely distributed in the Sonoran desert in Mexico. The Seri ethnic group in the Sonoran desert uses BM as an anti-inflammatory and painkiller drug for the treatment of sore throat, herpes labialis, abscessed tooth, and wound healing. Dried stems and leaves of BM are used in a tea to relieve painful urination and to stimulate bronchial secretion. Furthermore, BM is used for fighting venereal diseases. To investigate the effects of the hexane fraction of resin methanol extract (BM-H) on cell growth, the acute myeloid cell line (OCI-AML3) was treated with 250, 25, or 2.5 µg/mL of BM-H. The first 2 concentrations were able to significantly decrease OCI-AML3 cell number. This reduced cell number was associated with decreased S-phase, blockade of G2/M phase of the cell cycle, and increased cell death. Similar results were obtained on all tested tumor cell lines of different origins. We found that blockade of the cell cycle was a result of upregulation of p21 protein in a p53-independent way. Increase of p21 was possibly a result of upstream upregulation of p-ERK (which stabilizes p21 protein) and downregulation of p-38 (which promotes its degradation). Regarding cell death, activation of caspase-3, but not of caspase-8 or -9, was detectable after BM-H treatment. In conclusion, these data suggest that BM-H inhibited proliferation of cell lines mainly by a p21-dependent, p53-independent mechanism and promoted apoptosis through activation of caspase-3 but not caspase-8 or -9.
authors.affiliation: 1 Section of Pharmacology, Department of Medicine, University of Perugia, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Adorisio
authors.affiliation: 2 Infectivology and Clinical Trials Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
authors.affiliation: 3 Department of Pharmaceutical Sciences, University of Perugia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gigliarelli
authors.affiliation: 4 Section of Onco-hematology, S. Maria Terni Hospital, Department of Surgery and Medical Sciences, University of Perugia, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Muscari
authors.affiliation: 1 Section of Pharmacology, Department of Medicine, University of Perugia, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Cannarile
authors.affiliation: 4 Section of Onco-hematology, S. Maria Terni Hospital, Department of Surgery and Medical Sciences, University of Perugia, Italy.
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.affiliation: 3 Department of Pharmaceutical Sciences, University of Perugia, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Marcotullio
authors.affiliation: 1 Section of Pharmacology, Department of Medicine, University of Perugia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
authors.affiliation: 3 Department of Pharmaceutical Sciences, University of Perugia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Curini
authors.affiliation: 5 Department of Chemical and Biological Science University of Sonora, Hermosillo, Mexico.
authors.forename: Ramon Enrique
authors.initials: RE
authors.lastname: Robles Zepeda
authors.affiliation: 1 Section of Pharmacology, Department of Medicine, University of Perugia, Italy.|6 Foligno Nursing School, Department of Medicine, University of Perugia, Italy.
authors.forename: Domenico V
authors.initials: DV
authors.lastname: Delfino
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D031233:Bursera / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D045325:HCT116 Cells; D018922:HL-60 Cells; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D061986:MCF-7 Cells; D010936:Plant Extracts / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020298:U937 Cells
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D006586:Hexanes; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3
keywords: Bursera microphylla A Gray; Mexican traditional medicine; antiproliferative effect; human cancer cell lines; p21; proapoptotic effect