title: 7-Epiclusianone, a Benzophenone Extracted from Garcinia brasiliensis (Clusiaceae), Induces Cell Cycle Arrest in G1/S Transition in A549 Cells.
abstract: Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 μM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies.
authors.affiliation: Institute of Biomedical Sciences, Federal University of Alfenas, 37130-000 Alfenas, Brazil. marisaionta@gmail.com.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ionta
authors.affiliation: Institute of Biomedical Sciences, Federal University of Alfenas, 37130-000 Alfenas, Brazil. alfer_gui@hotmail.com.
authors.forename: Guilherme A
authors.initials: GA
authors.lastname: Ferreira-Silva
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 São Paulo, Brazil. eloniero@yahoo.com.
authors.forename: Evandro L
authors.initials: EL
authors.lastname: Niero
authors.affiliation: Institute of Chemistry, Federal University of Alfenas, 37130-000 Alfenas, Brazil.
authors.forename: Éderson D'Martin
authors.initials: ÉD
authors.lastname: Costa
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 São Paulo, Brazil. adam.arai@gmail.com.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Martens
authors.affiliation: Institute of Chemistry, Federal University of Alfenas, 37130-000 Alfenas, Brazil. welton_rosa@hotmail.com.
authors.forename: Welton
authors.initials: W
authors.lastname: Rosa
authors.affiliation: Institute of Chemistry, Federal University of Alfenas, 37130-000 Alfenas, Brazil. marisigs@gmail.com.
authors.forename: Marisi G
authors.initials: MG
authors.lastname: Soares
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Gláucia M
authors.initials: GM
authors.lastname: Machado-Santelli
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo, 09920-000 Diadema, Brazil. joao.lago@unifesp.br.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
authors.affiliation: Institute of Chemistry, Federal University of Viçosa, 36570-900 Viçosa, Brazil. marcelo_hs@yahoo.com.br.
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Santos
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005638:Fruit / Q000737:chemistry*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D029760:Garcinia / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C118110:7-epiclusianone; D000972:Antineoplastic Agents, Phytogenic; D001577:Benzophenones; D016227:Benzoquinones; D010936:Plant Extracts
keywords: 7-epiclusianone; Garcinia brasiliensis; antiproliferative activity; cell cycle arrest; cell death; lung cancer