Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum

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.

Marine natural products

“…It also induced apoptosis and suppressed metastasis. 245 Phthalide derivatives 376 (ref. 246) (rst time MNP) and 377, isopatulin 247 378 (rst time MNP), 248 and oxindole alkaloids 379-386 were also isolated from the Penicillium genus.…”

The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms

“…The fermentation broth of the mangrove soil-derived fungus Aspergillus sp. OUCMDZ-1914 yielded two 3-oligoenoyltetramic acids, RKB-3884A (27) and its analogue 18-OH-RKB-3884A (28). Molecule 27 showed potent inhibition of the H1N1 influenza virus (IC50 = 116.2 μM), equal to the positive control ribavirin (IC50 = 138.1 μM ) [33].…”

“…Tirandamycins (TAMs) are a subgroup of Streptomyces-derived 3-dienoyltetramic acid antibiotics that exhibit broad biological activities, such as bacterial RNA polymerase inhibition [34], The fermentation broth of the mangrove soil-derived fungus Aspergillus sp. OUCMDZ-1914 yielded two 3-oligoenoyltetramic acids, RKB-3884A (27) and its analogue 18-OH-RKB-3884A (28). Molecule 27 showed potent inhibition of the H1N1 influenza virus (IC 50 = 116.2 µM), equal to the positive control ribavirin (IC 50 = 138.1 µM) [33].…”

“…Chemical structures of 3-oligoenoyltetramic acids(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

“…PBMCs (5x10 6 /ml) isolated from patients with LC and healthy donors were stimulated with rMBP-NAP (0.2 mg/ml) for 10 days, and used as the effector cells. EC-9706 and K562 were originally obtained from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China) and were cultured in Iscove's modified Dulbecco's medium supplemented with 10% inactivated fetal calf serum (both from Thermo Fisher Scientific, Inc.) with 5% CO 2 at 37˚C, which were used as target cells (16,17). EC-9706/K562 (5x10 3 cells/well) were co-cultured with various densities (6.25x10 4 , 1.25x10 5 and 2.5x10 5 ) of effector cells (PBMCs) at 37˚C for 4 h. The following effector: Target cell ratios were used: 12.5:1, 25:1 and 50:1.…”