RESUMO
3- and 10-Bromofascaplysins was previously found to possess cytotoxic activity. In this study, we investigated their cancer preventive and proapoptotic properties. These effects were tested on mouse skin epidermal JB6 P(+) Cl41 cell line, its stable transfectants, and human tumor HL-60, THP-1, SNU-C4, SK-MEL-28, DLD-1, MDA-MB-231, and HeLa cells using a variety of assessments, including a cell viability (MTS) assay, flow cytometry, anchorage-independent soft agar assay, luciferase assay, mitochondrial permeability assay, and Western blotting. 3- and 10-Bromofascaplysins were effective at submicromolar concentrations as the anticancer agents, which exerted their action, at least in part, through the induction of caspase-8, -9, -3-dependent apoptosis.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Animais , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Mitocôndrias/metabolismo , Permeabilidade/efeitos dos fármacos , Pele/citologiaRESUMO
BACKGROUND: 3-Demethylubiquinone Q2 (3DMUbQ2), isolated from the ascidian Aplidium glabrum and later synthesized, is known as a natural product inhibiting EGF-induced malignant JB6 P+ Cl 41 cell transformation. However, its in vivo anticancer properties and probable mechanism of this action have not been studied. MATERIALS AND METHODS: Preventive and curable effects of3DMUbQ2 on mice with inoculated Ehrlich carcinoma tumors were examined by magnetic resonance tomography. Capability to inhibit human tumor cell colony growth and induce their apoptosis was investigated using the anchorage-independent phenotype expression assay in soft agar and flow cytometry. RESULTS: 3DMUbQ2 inhibits the growth of the solid Ehrlich carcinoma in mice, especially using the prophylactic scheme of administration (50% inhibition). It inhibits the phenotype expression of HT-460, HCT-116 and SK-MEL-28 human tumor cells and induces apoptosis of these cell lines, as well as that of HL-60 and THP-1 tumor cells. CONCLUSION: 3DMUbQ2 and other related marine polyprenylquinones have potential for development of a new antitumor agent in cancer prophylactics and treatment and should be further investigated.