Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro

Abstract

Novel strategies to treat cancer effectively without adverse effects on the surrounding normal tissue are urgently needed. Marine sponges provide a natural and renewable source of promising anti-tumor agents. Here, we investigated the anti-tumor activity of Aerothionin and Homoaerothionin, two bromotyrosines isolated from the marine demosponge Aplysina cavernicola, on two mouse pheochromocytoma cells, MPC and MTT. To determine the therapeutic window of these metabolites, we furthermore explored their cytotoxicity on cells of the normal tissue. Both metabolites diminished the viability of the pheochromocytoma cell lines significantly from a concentration of 25 µM under normoxic and hypoxic conditions. Treatment of MPC cells leads moreover to a reduction in the number of proliferating cells. To confirm the anti-tumor activity of these bromotyrosines, 3D-pheochromocytoma cell spheroids were treated with 10 µM of either Aerothionin or Homoaerothionin, resulting in a significant reduction or even complete inhibition of the spheroid growth. Both metabolites reduced viability of normal endothelial cells to a comparable extent at higher micromolar concentration, while the viability of fibroblasts was increased. Our in vitro results show promise for the application of Aerothionin and Homoaerothionin as anti-tumor agents against pheochromocytomas and suggest acceptable toxicity on normal tissue cells.

Marine biomimetics: bromotyrosines loaded chitinous skeleton as source of antibacterial agents

“…Functionally, they are recognized as multitarget drugs [ 29 , 30 ], with prominent antiviral, antibacterial, antifungal, cytotoxic as well as antifouling activities (see for overview [ 31 – 42 ]). Some of poriferan bromotyrosines showed antimetastatic activity [ 43 , 44 ] as well as have been reported as effective inhibitors of acetylcholinesterase (AChE), that is a clinical marker of Alzheimer’s disease [ 45 ].…”

Synthesis and Cytotoxicity Evaluation of Spirocyclic Bromotyrosine Clavatadine C Analogs

“…Furthermore, moderate activity against MCF7, MDA-MB-231 (breast), and A549 (lung) cancer cell lines have been observed for clavatadine C 1 - TFA [ 10 ]. Marine bromotyrosines with an isoxazoline moiety attached to the spiro center have exhibited anticancer properties [ 11 , 12 ]. The spirocyclic bromotyrosine is structurally more rigid and better occupies the chemical space than the open-chain bromotyrosine, making it an interesting scaffold for medicinal chemistry [ 13 ].…”

Functionalization of 3D Chitinous Skeletal Scaffolds of Sponge Origin Using Silver Nanoparticles and Their Antibacterial Properties

“…These unique defense strategies, based on Br-containing secondary metabolite production, allowed this organism to survive more than 500 millions of years [37]. Today, bromotyrosines are recognized as multi-targeted marine drugs with broad fields of applications (i.e., as antitumorigenic and antimetastatic agents [55,56]). In order to isolate pure chitinous scaffolds from verongiid demosponges, diverse methodological approaches based on chemical, electrochemical and enzymatic treatments were reported (see for overview [36,57]).…”