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.
While advanced melanoma remains one of the most challenging cancers, recent developments in our understanding of the molecular drivers of this disease have uncovered exciting opportunities to guide personalized therapeutic decisions.,Genetic analyses of melanoma have uncovered several key molecular pathways that are involved in disease onset and progression, as well as prognosis.,These advances now make it possible to create a “Molecular Disease Model” (MDM) for melanoma that classifies individual tumors into molecular subtypes (in contrast to traditional histological subtypes), with proposed treatment guidelines for each subtype including specific assays, drugs, and clinical trials.,This paper describes such a Melanoma Molecular Disease Model reflecting the latest scientific, clinical, and technological advances.