Cell cycle arrest through inhibition of tubulin polymerization by withaphysalin F, a bioactive compound isolated from Acnistus arborescens.

Danilo D Rocha, Aruna Balgi, Ana Isabel V Maia, Otilia D Pessoa, Edilberto R Silveira, Letícia V Costa-Lotufo, Michel Roberge, Claudia Pessoa

Laboratório de Oncologia Experimental, Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil.

Investigational new drugs 2012 Jun

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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.

Citation

Danilo D Rocha, Aruna Balgi, Ana Isabel V Maia, Otilia D Pessoa, Edilberto R Silveira, Letícia V Costa-Lotufo, Michel Roberge, Claudia Pessoa. Cell cycle arrest through inhibition of tubulin polymerization by withaphysalin F, a bioactive compound isolated from Acnistus arborescens. Investigational new drugs. 2012 Jun;30(3):959-66