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

0467237 - ÚEB 2017 RIV GB eng J - Článek v odborném periodiku
Pachnikova, G. - Uldrijan, S. - Imramovský, A. - Kryštof, Vladimír - Slaninová, I.
Substituted 2-hydroxy-N-(arylalkyl)benzamide sensitizes cancer cells to metabolic stress by disrupting actin cytoskeleton and inhibiting autophagic flux.
Toxicology in Vitro. Roč. 37, DEC (2016), s. 70-78. ISSN 0887-2333. E-ISSN 1879-3177
Institucionální podpora: RVO:61389030
Klíčová slova: hepatocellular-carcinoma cells * sorafenib * apoptosis * death * maturation * membrane * melanoma * Actin * Autophagy * Melanoma * Metabolic stress * Sorafenib * Substituted 2-hydroxy-N-(arylalkyl)benzamide
Kód oboru RIV: CE - Biochemie
Impakt faktor: 2.866, rok: 2016

N-((R)-1-(4-chlorophenylcarbamoy1)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (Compound 6k), was recently isolated during the preparation of amino adds 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 adlision, 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.
Trvalý link: http://hdl.handle.net/11104/0265350