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

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Publikace nespadá pod Pedagogickou fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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PÁCHNIKOVÁ Gabriela ULDRIJAN Stjepan IMRAMOVSKÝ Aleš KRYŠTOF Vladimír SLANINOVÁ Iva

Rok publikování 2016
Druh Článek v odborném periodiku
Časopis / Zdroj Toxicology in Vitro
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.1016/j.tiv.2016.09.006
Obor Genetika a molekulární biologie
Klíčová slova Actin; Autophagy; Melanoma; Metabolic stress; Sorafenib; Substituted 2-hydroxy-N-(arylalkyl)benzamid
Popis 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.
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