Biological Activities of Cyclic and Acyclic B-Type Laxaphycins in SH-SY5Y Human Neuroblastoma Cells.

Marine Drugs
Rebeca AlvariñoLuis M Botana

Abstract

Laxaphycins are a family of non-ribosomal lipopeptides that have been isolated from several cyanobacteria. Some of these compounds have presented cytotoxic activities, but their mechanism of action is poorly understood. In this work, the already described laxaphycins B and B3, and acyclolaxaphycins B and B3 were isolated from the marine cyanobacteria Anabaena torulosa. Moreover, two new acyclic compounds, [des-(Ala4-Hle5)] acyclolaxaphycins B and B3, were purified from the herviborous gastropod Stylocheilus striatus, with this being the first description of biotransformed laxaphycins. The structure of these new compounds was elucidated, together with the absolute configuration of acyclolaxaphycins B and B3. The bioactivities of the six peptides were determined in SH-SY5Y human neuroblastoma cells. Laxaphycins B and B3 were cytotoxic (IC50: 1.8 and 0.8 µM, respectively) through the induction of apoptosis. In comparison, acyclic laxaphycins did not show cytotoxicity but affected mitochondrial functioning, so their effect on autophagy-related protein expression was analyzed, finding that acyclic peptides affected this process by increasing AMPK phosphorylation and inhibiting mTOR. This work confirms the pro-apoptotic properties of...Continue Reading

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Citations

Sep 25, 2020·Marine Drugs·Sergey A Dyshlovoy
Jun 2, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Nadia Pérez-FuentesLuis M Botana
Jun 5, 2021·Organic & Biomolecular Chemistry·Lassi Matti Petteri HeiniläKaarina Sivonen
Jun 20, 2021·Physiologia Plantarum·David P FewerLars Herfindal

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Methods Mentioned

BETA
NMR
nuclear magnetic resonance
flow cytometry
light scattering
Assay

Software Mentioned

Graph Pad Prism
IDEAS Application
Diversity GeneSnap system
Syngene

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