Natural Products and Bioprospecting    2020, Vol. 10 Issue (6) : 367-375     DOI: 10.1007/s13659-020-00268-8
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Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species
Christian Bailly
OncoWitan, 59290 Lille(Wasquehal), France
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Abstract  Nagilactones are tetracyclic natural products isolated from various Podocarpus species. These lactone-based compounds display a range of pharmacological effects, including antifungal, anti-atherosclerosis, anti-inflammatory and anticancer activities reviewed here. The most active derivatives, such as nagilactones C, E and F, exhibit potent anticancer activities against different cancer cell lines and tumor models. A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i) a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis, (ii) a blockade of the epithelial to mesenchymal cell transition contributing to an inhibition of cancer cell migration and invasion and (iii) a capacity to modulate the PD-L1 immune checkpoint. Different molecular effectors have been implicated in the antitumor activity, chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis. Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases, such as RIOK2 and JAK2, has been postulated with Nag-E. The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids. The mechanistic analysis also provides useful information for structurally related compounds (podolactones, oidiolactones, inumakilactones) isolated from Podocarpus plants.
Keywords Cancer      Natural products      Mechanism of action      Molecular target      Terpenoids     
Corresponding Authors: Christian Bailly     E-mail: christian.bailly@oncowitan.com
Issue Date: 24 December 2020
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Christian Bailly. Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species[J]. Natural Products and Bioprospecting, 2020, 10(6): 367-375.
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http://npb.kib.ac.cn/EN/10.1007/s13659-020-00268-8     OR     http://npb.kib.ac.cn/EN/Y2020/V10/I6/367
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