Abstract
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.
Highlights
Malignant melanoma is one of the few cancers that have displayed an increasing incidence and, more importantly, a steady mortality rate over the past decade [1,2]
The results showed that apoptosis rates of A-375 cells changed from 45.80%, 55.58% to 91.36% when treated with 12.5 μM, 25 μM and 50 μM of penicitrinine A (Figure 7)
This study investigated a new compound penicitrinine A isolated and identified from marine fungus
Summary
Malignant melanoma is one of the few cancers that have displayed an increasing incidence and, more importantly, a steady mortality rate over the past decade [1,2]. Even if surgery represents the cure in the early phase of disease, the prognosis in the metastatic phase remains very poor. Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma [3]. Chemotherapy remains an essential treatment option [4]. Recurrence/metastasis is the major cause of death in patients with malignant melanoma cancer. Novel potent drugs, especially anti-metastasis drugs, would be urgently needed for the treatment of refractory or relapsing melanoma cancer patients [5]
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