Aaptamines from the Marine SpongeAaptossp. Display Anticancer Activities in Human Cancer Cell Lines and Modulate AP-1-, NF-κB-, and p53-Dependent Transcriptional Activity in Mouse JB6 Cl41 Cells

Abstract

Aaptamine (8,9-dimethoxy-1H-benzo[de][1,6]naphthyridine) is a marine natural compound possessing antioxidative, antimicrobial, antifungal, and antiretroviral activity. Earlier, we have found that aaptamine and its derivatives demonstrate equal anticancer effects against the human germ cell cancer cell lines NT2 and NT2-R and cause some changes in the proteome of these cells. In order to explore further the mechanism of action of aaptamine and its derivatives, we studied the effects of aaptamine (1), demethyl(oxy)aaptamine (2), and isoaaptamine (3) on human cancer cell lines and on AP-1-, NF-κB-, and p53-dependent transcriptional activity in murine JB6 Cl41 cells. We showed that compounds 1–3 demonstrate anticancer activity in THP-1, HeLa, SNU-C4, SK-MEL-28, and MDA-MB-231 human cancer cell lines. Additionally, all compounds were found to prevent EGF-induced neoplastic transformation of murine JB6 Cl41 cells. Nuclear factors AP-1, NF-κB, and p53 are involved in the cellular response to high and nontoxic concentrations of aaptamine alkaloids 1–3. Furthermore, inhibition of EGF-induced JB6 cell transformation, which is exerted by the compounds 1–3 at low nontoxic concentrations of 0.7–2.1 μM, cannot be explained by activation of AP-1 and NF-κB.

Bioactividad de las esponjas marinas Cliona varians y Cinachyrella kuekenthali provenientes de Isla Larga, Bahía de Mochima, Estado Sucre, Venezuela / Bioactivity of Cliona varians and Cinachyrella kuekenthali marine sponges from Isla Larga, Mochima Bay, Sucre state, Venezuela

“…subsistir en este ecosistema. Se detectaron alcaloides en ambas especies, lo cual concuerda con los trabajos reportados anteriormente en la literatura, en los que se ha aislado aaptaminas en el género Aaptos (Dyshlovoy et al, 2014), una variedad de alcaloides tipo bromotirosina en esponjas del género Aplysina, cinachyramino en el género Cinachyrella, halitoxina en A. viridis, reportándose por primera vez la presencia general de alcaloides en esponjas +++: Actividad fuerte (diámetro superior a 18 mm), ++: Actividad moderada (diámetro entre 15-18 mm), +: Actividad leve (diámetro entre 11-14 mm), -: no hubo actividad, %MSE: porcentaje de microrganismos sensibles a cada extracto, %EAM: porcentaje de extractos activos contra un mismo microrganismo. Estudio realizado con una concentración de 40 mg/ml y discos de 5 mm de diámetro.…”

Achievements in the Study of Marine Low‐Molecular Weight Biologically Active Metabolites from the Vietnamese Territorial Waters as a Result of Expeditions aboard the Research Vessel ‘Akademik Oparin’ (2004–2017)

“…[77] Collection of new samples of Aaptos genus in the Vietnamese waters and following bioassay-guided fractionation (cytotoxicity toward HL-60 cells) allowed to isolate four new compounds with antitumor and cancer-preventive activities toward [44,45] In addition, mechanisms of these bioactivities were investigated in detail. [47] Sponges of Penares genus are source of metabolites with various bioactivities including antitumor activity. The sample of the Penares sp.…”

“…All these compounds interfered with the EGFinduced neoplastic transformation of JB6 Cl 41 cells. [47] The effects of compounds 119, 123, and 124 on the cisplatin-sensitive (NT-2) and cisplatin-resistant (NT2-R) human embryonic carcinoma cell line were also studied. [48] Three new polar steroids, topsentiasterol sulfate F (125) and the first reported chlorine-and iodinecontaining sulfated steroids chlorotopsentiasterol sulfate D (126) and iodotopsentiasterol sulfate D (127) were isolated from the marine sponge Topsentia sp.…”

Isoaaptamine Induces t-47D Cells Apoptosis and Autophagy via Oxidative Stress

“…Several reports emphasized the cytotoxic effect of aaptamine analogs through the modulation of AP-1, NFκB and p53-dependent transcriptional activity in mouse JB6 Cl41 cells and cisplatinresistant germ cancer cells [20,21]. In this study, we found that the major active alkaloid, IAp, demonstrated potent cytotoxicity against several breast cancer cell lines, T-47D, MCF-7 and MDA-MB-231 with promising IC50 values (Table 1) and induced autophagy and apoptosis of T-47D cells (Figures 2 and 3).…”