RESUMEN
Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.
Asunto(s)
Alcaloides/farmacología , Antineoplásicos/farmacología , Organismos Acuáticos/metabolismo , Penicillium/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
A rare hexacyclic oxindole alkaloid, speradine F (1), together with two novel tetracyclic oxindole alkaloids, speradines G (2) and H (3), were isolated from the marine-derived fungus Aspergillus oryzae. Their structures were determined by spectroscopic methods and X-ray diffraction analysis. This study is the first report on cyclopiazonic acid (CPA)-type alkaloids with a hexacyclic skeleton.