P38-beta/SAPK-inhibiting and apoptosis-inducing activities of (E)-4-chloro-2-((3-ethoxy-2-hydroxybenzylidene) amino)phenol
Yükleniyor...
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Sage Publications LTD
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
The present study has three purposes; first evaluating cytotoxicity of (E)-4-chloro-2-((3-ethoxy-2-hydroxybenzylidene)amino)phenol (ACES), second deciphering ACES-mediated cellular death mechanism, and third estimating ACES-mediated alterations in the expressions of mitogen-activated protein kinase (MAPK) pathway-related genes. Neutral red uptake assay, cell cycle analysis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) measurements, caspase 3/7 and 9 activations, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were implemented. IC50 values of ACES-treated five cells were around 4-6 mu g/mL. However, Caco-2 and Huh-7 cells were found to be twofold resistant and fivefold sensitive with IC50 values of 11 mu g/mL and 0.93 mu g/mL, respectively. In this study, it was initially reported that ACES exhibits selective cytotoxicity to Huh-7 cells. In addition, ACES induced apoptosis by nuclear fragmentation, MMP disruption, and intracellular ROS elevation in MCF-7 cells. qRT-PCR experiment indicated the expressions of 30 genes including ATF2, CREB1, MYC, NFATC4 (NFAT3), CCNA1, CCNB1, CCND2, CDK2, CDKN1A (p21CIP1), CDKN1C (p57KIP2), CDKN2A (p16INK4a), CDKN2B (p15INK4b), DLK1, NRAS, CDC42, PAK1, MAP4K1 (HPK1), MAP3K3 (MEKK3), MAP2K3 (MEK3), MAP2K6 (MEK6), MOS, MAPK1 (ERK2), MAPK8 (JNK1), MAPK10 (JNK3), MAPK11 (p38-beta), LAMTOR3 (MP1), MAPK8IP2 (JIP-1), PRDX6 (AOP2), COL1A1, and HSPA5 (Grp78) were downregulated at least 1.5-fold. Moreover, ACES effectively inhibited expressions of genes that code for elements of p38-beta/stress-activated protein kinase (SAPK) pathway. ACES has the potential to be used for the reversal of trastuzumab resistance in breast cancer patients by inhibiting p38/SAPK pathway in MCF-7 cells. Therefore, with the selective cytotoxic, apoptosis-inducing, and p38-beta/SAPK-inhibiting activities, ACES can be utilized for developing a novel anticancer drug.
Açıklama
WOS:000534108600001
PubMed ID: 32394730
Anahtar Kelimeler
P38-β/SAPK Pathway, Apoptosis, Chemoresistance, Schiff Bases
Kaynak
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
Sayı
Künye
Karaosmanoğlu, O. (2020). P38-β/SAPK-inhibiting and apoptosis-inducing activities of (E)-4-chloro-2-((3-ethoxy-2-hydroxybenzylidene) amino)phenol. Human and Experimental Toxicology, May 2020- 1-16 ss.
