title: Cell cycle arrest through inhibition of tubulin polymerization by withaphysalin F, a bioactive compound isolated from Acnistus arborescens.
abstract: Many compounds used in the treatment of cancer possess tubulin-interacting properties that lead to mitotic arrest. Withaphysalins are potent cytotoxic compounds that are commonly found in plants belonging to the Solanaceae family, such as Acnistus arborescens; however, the cytotoxic mechanisms or molecular targets of these compounds remain unknown. Thus, the aim of this study was to evaluate the effects of whitaphysalins on cancer cell cycle progression and tubulin interaction. In this report, we show the antiproliferative activity of withaphysalin F and its effect in arresting cells in the G(2)/M phase of the cell cycle. These two effects are the result of the interference of withaphysalin F in the polymerization of microtubules. Withaphysalin F also induced DNA fragmentation, which can be related to an increase in mitochondrial membrane depolarization. These results suggest that interference of withaphysalin F in microtubule polymerization may induce cell cycle arrest in the G(2)/M phase and therefore contribute to growth inhibition of tumor cells in vitro. Taken together, these studies indicate that withaphysalin F could potentially be used as an anticancer drug.
authors.affiliation: Laboratório de Oncologia Experimental, Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil.
authors.forename: Danilo D
authors.initials: DD
authors.lastname: Rocha
authors.forename: Aruna
authors.initials: A
authors.lastname: Balgi
authors.forename: Ana Isabel V
authors.initials: AI
authors.lastname: Maia
authors.forename: Otilia D
authors.initials: OD
authors.lastname: Pessoa
authors.forename: Edilberto R
authors.initials: ER
authors.lastname: Silveira
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Michel
authors.initials: M
authors.lastname: Roberge
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012632:Secosteroids / Q000494:pharmacology*; D019657:Solanaceae; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012632:Secosteroids; D014404:Tubulin; C488716:withaphysalin F; D004875:Ergosterol