Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

KAUEROVÁ, Tereza, J KOS, Tomáš GONĚC, J JAMPILEK a Peter KOLLÁR. Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines. International Journal of Molecular Sciences. Basel, Switzerland: MDPI AG, 2016, roč. 17, č. 8, 14 s. ISSN 1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms17081219.

Základní údaje

• Originální název: Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines
• Autoři: KAUEROVÁ, Tereza, J KOS, Tomáš GONĚC, J JAMPILEK a Peter KOLLÁR.
• Vydání: International Journal of Molecular Sciences, Basel, Switzerland, MDPI AG, 2016, 1422-0067.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Utajení: není předmětem státního či obchodního tajemství
• Impakt faktor: Impact factor: 3.226
• Doi: http://dx.doi.org/10.3390/ijms17081219
• UT WoS: 000382337900033
• Klíčová slova anglicky: hydroxynaphthanilides; salicylanilides; cell proliferation; apoptosis; anticancer effect
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of salicylanilides, compounds possessing a wide range of pharmacological activities, including promising anticancer properties. The aim of this study was to evaluate the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides with a special focus on structure-activity relationships. The antiproliferative effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1) assay, and cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay. Protein expression was estimated by Western blotting. Our data indicate that the potential to cause the antiproliferative effect increases with the shift of the nitro substituent from the ortho-to the para-position. The most potent compounds, 3-hydroxy-N-(3-nitrophenyl) naphthalene-2-carboxamide (2), and 2-hydroxy-N-(4-nitrophenyl)-naphthalene-1-carboxamide (6) showed antiproliferative activity against THP-1 and MCF-7 cancer cells without affecting the proliferation of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1 and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1 protein levels, while the levels of cyclin B1 were not affected. Moreover, compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These results suggest that hydroxynaphthanilides might represent a potential model structure for the development of novel anticancer agents.