Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors

Abstract

Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P+ cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed.

The Extracts of Some Marine Invertebrates and Algae Collected off the Coast Waters of Vietnam Induce the Inhibitory Effects on the Activator Protein‐1 Transcriptional Activity in JB6 Cl41 Cells

“…In continuation of our search for cancer preventive compounds from marine organisms [32,33,38,43,44], we studied the in�uence of the extracts from 148 species of marine invertebrates and algae on the AP-1-dependent transcriptional activity in mouse epidermal JB6 Cl41 cells. e JB6 Cl41 cells undergo the malignant transformation under the treatment of EGF as a promoter.…”

“…Activity. e effect of the studied substances on AP-1 transcriptional activation was investigated in JB6 Cl41 cells stably expressing a luciferase reporter gene controlled by an AP-1 DNA binding sequence as described earlier [43]. In brief, viable JB6 Cl41 AP-1cells (8×10 3 ) suspended in 100 L of 5% FBS/MEM were added into each well of a 96-well plate.…”

Anti‐migratory activity of marine alkaloid monanchocidin A – proteomics‐based discovery and confirmation

“…Preparation of protein extracts for two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) and Western blotting was performed as described previously . In brief, for Western blotting 1 × 10 6 cells/well were seeded in ø 6 cm TC dishes (Sarstedt, Numbrecht, Germany) in 10 mL of media per dish, incubated overnight and treated with MonA for 48 h in 5 mL of media per dish; for 2D‐PAGE, 2 × 10 6 cells/well were seeded in culture flasks (TC Flask T75, Sarstedt), incubated overnight, and treated with MonA for 48 h in 20 mL of media per flask.…”

Absolute Configuration and Body Part Distribution of the Alkaloid 6-epi-Monanchorin from the Marine Polychaete Chaetopterus variopedatus

“…Colony formation assay was performed as described before with slight modifications [33]. Cells were treated with the compound for 48 h, then cells were trypsinized and the number of living cells was counted with the trypan blue exclusion assay, as described before [34]. One hundred viable cells were plated into each well of 6-well plates in complete drug-free media (3 mL/well) and were incubated for 14 days.…”