2. Academic Validation
  3. Substituted 2-hydroxy-N-(arylalkyl)benzamide sensitizes cancer cells to metabolic stress by disrupting actin cytoskeleton and inhibiting autophagic flux

Substituted 2-hydroxy-N-(arylalkyl)benzamide sensitizes cancer cells to metabolic stress by disrupting actin cytoskeleton and inhibiting autophagic flux

  • Toxicol In Vitro. 2016 Dec:37:70-78. doi: 10.1016/j.tiv.2016.09.006.
Gabriela Páchniková 1,  Stjepan Uldrijan 1,  Aleš Imramovský 2,  Vladimír Kryštof 3,  Iva Slaninová 4
Affiliations

Affiliations

  • 1 Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Pekařská 53, 656 91 Brno, Czech Republic.
  • 2 Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
  • 3 Laboratory of Growth Regulators, Faculty of Science, Palacky University and Institute of Experimental Botany ASCR, Šlechtitelů 27, 78371 Olomouc, Czech Republic.
  • 4 Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. Electronic address: ipokorna@med.muni.cz.
PMID: 27612957 DOI: 10.1016/j.tiv.2016.09.006
Abstract

N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (Compound 6k), was recently isolated during the preparation of Amino acids esters with salicylanilides. We show here that 6k disrupts the dynamics of actin Cytoskeleton in human melanoma cells, affecting processes essential for the maintenance and expansion of tumours such as cell adhesion, motility, proliferation, vesicular transport, and autophagic flux. We demonstrated that inhibition of Autophagy by 6k increased the sensitivity of melanoma cells to metabolic stress induced by rotenone or nutrient starvation and potentiated the anti-proliferative activity of small molecule multikinase inhibitor sorafenib. Since Autophagy plays an important role in survival of Cancer cells subjected to chemotherapy, the above mentioned properties are interesting from clinical point of view as 6k could promote metabolic stress within the tumour microenvironment and potentiate the effect of cytostatics in combination therapy.

Keywords

Actin; Autophagy; Melanoma; Metabolic stress; Sorafenib; Substituted 2-hydroxy-N-(arylalkyl)benzamide.

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