RESUMO
Activity-guided fractionation of a petroleum ether-soluble extract of the roots of Onosma paniculata, which has been shown to affect the cell cycle and to induce apoptosis in melanoma cells, led to the isolation of several shikonin derivatives, namely, ß-hydroxyisovalerylshikonin (1), acetylshikonin (2), dimethylacrylshikonin (3), and a mixture of α-methylbutyrylshikonin and isovalerylshikonin (4+5). All compounds exhibited strong cytotoxicity against eight cancer cell lines and MRC-5 lung fibroblasts, with 3 found to possess the most potent cytotoxicity toward four melanoma cell lines (SBcl2, WM35, WM9, and WM164). Furthermore, 3 and the mixture of 4+5 were found to interfere with cell-cycle progression in these cell lines and led to an increasing number of cells in the subG1 region as well as to caspase-3/7 activation, indicating apoptotic cell death.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Boraginaceae/química , Ciclo Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Naftoquinonas/isolamento & purificação , Naftoquinonas/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/efeitos dos fármacos , Caspase 7/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Humanos , Melanoma , Estrutura Molecular , Naftoquinonas/química , Raízes de Plantas/químicaRESUMO
AIM OF THE STUDY: Traditional Chinese medicine (TCM) has become very popular in Western countries during the last years. Zicao, a remedy of TCM, has been traditionally used to treat cancer, and, its main constituents, naphthoquinones, have been reported to possess antitumor activity (Chen et al., 2002; Papageorgiou et al., 1999). Here, we prepared extracts of different polarities of Onosma paniculatum Bur. & Franch., a plant which is amongst others used as Zicao, but, much less investigated. The extracts were analyzed concerning their growth inhibitory and apoptosis-inducing activity in various tumor cells. MATERIALS AND METHODS: Cell viability was measured by XTT viability and a growth inhibition assay. Effects on the cell cycle and caspase-3 were determined by flow cytometry. RESULTS: From three different extracts, a petrol ether extract showed significant growth inhibitory effect, cell cycle influence and caspase-3 dependent induction of apoptosis which was time and dose dependent. CONCLUSION: To further determine the activity and mechanism of action of the petrol ether extract, we would like to isolate and identify the active principle and investigate the effects in more detail.