Effects and Mechanisms of Action of Preussin, a Marine Fungal Metabolite, against the Triple-Negative Breast Cancer Cell Line, MDA-MB-231, in 2D and 3D Cultures

Abstract

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer (BC) with a typically poorer prognosis than other subtypes of BC and limited therapeutic options. Therefore, new drugs would be particularly welcome to help treat TNBC. Preussin, isolated from the marine sponge-associated fungus, Aspergillus candidus, has shown the potential to reduce cell viability and proliferation as well as to induce cell death and cell cycle arrest in 2D cell culture models. However, studies that better mimic the tumors in vivo, such as 3D cell cultures, are needed. Here, we studied the effects of preussin in the MDA-MB-231 cell line, comparing 2D and 3D cell cultures, using ultrastructural analysis and the MTT, BrdU, annexin V-PI, comet (alkaline and FPG modified versions), and wound healing assays. Preussin was found to decrease cell viability, both in 2D and 3D cell cultures, in a dose-dependent manner, impair cell proliferation, and induce cell death, therefore excluding the hypothesis of genotoxic properties. The cellular impacts were reflected by ultrastructural alterations in both cell culture models. Preussin also significantly inhibited the migration of MDA-MB-231 cells. The new data expanded the knowledge on preussin actions while supporting other studies, highlighting its potential as a molecule or scaffold for the development of new anticancer drugs against TNBC.

Visualization of the relationship between fungi and cancer from the perspective of bibliometric analysis

“…can inhibit the proliferation and migration of tumor cells by inducing apoptosis and autophagy, offering a promising strategy for cancer therapy [ 122 , 123 ]. To fully evaluate the potential of fungal metabolites as anticancer agents, a combination of in vitro and in vivo studies is necessary [ 40 , [124] , [125] , [126] ]. Molecular docking techniques can also be employed to predict the potential binding modes and affinity of these compounds to their target proteins [ 79 , 82 , 88 ].…”

“…While research advancements have highlighted the significant role of fungi in cancer etiology, the underlying mechanisms governing the interplay between fungi and cancer remain elusive [ 28 , [37] , [38] , [39] , [40] ]. Therefore, further scientific inquiry is essential to identify specific fungal species and their associated mechanisms contributing to cancer progression.…”

Advances on anticancer fungal metabolites: sources, chemical and biological activities in the last decade (2012–2023)

“…Preussin ( 273 ), in a dose-dependent manner decreased cell viability, both in 2D and 3D cell cultures, impair cell proliferation, and caused cell death, excluding the hypothesis of genotoxic properties. Preussin ( 273 ) also strongly inhibited the migration of MDA-MB-231 cells [ 139 ].…”

Redox-neutral α-functionalization of pyrrolidines: facile access to α-aryl-substituted pyrrolidines

“…Alkylated pyrrolidine (+)-preussin was an antibacterial and anticancer alkaloid from the fermentation broth of bacterium Aspergillus ochraceus . 3 Anisomycin is an antibiotic drug that inhibits bacterial protein and DNA synthesis. 4 Simple arylated pyrrolidines such as nicotine have strong bioactivity.…”