Abstract
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 µg/mL. However, Caco-2 and Huh-7 cells were found to be twofold resistant and fivefold sensitive with IC50 values of 11 µg/mL and 0.93 µg/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-β), 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-β/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-β/SAPK-inhibiting activities, ACES can be utilized for developing a novel anticancer drug.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
