Abstract
BackgroundGastric cancer, as a multifactorial disorders, shows cytological and architectural heterogeneity compared to other gastrointestinal cancers, making it therapeutically challenging. Cisplatin is generally used in clinic for gastric cancer treatment but with toxic side effects and develops resistance. Anti-tumor properties of copper and its coordinated compounds have been explored intensively in recent years.MethodsIn this study, we synthesized a novel Schiff base copper coordinated compound (SBCCC) and examined its antitumor effects in two gastric cancer cell lines SGC-7901 and BGC-823 as well as a mouse model of gastric cancer.ResultsThe results show that SBCCC can significantly inhibit the proliferation of gastric cancer cells in a dose- and time-dependent manner. The IC50 of SBCCC in SGC-7901 and BGC-823 cells is 1 μM, which is much less than cisplatin’s IC50. SBCCC induces apoptosis and causes cell cycle arrest at the G1 phase. SBCCC induces apoptosis via multiple pathways including inhibition of NF-κB, ROS production and autophagy.ConclusionsThe synthesized SBCCC induced cancer cell death via inhibition of NF-κB, ROS production and autophagy. The multiple cell-killing mechanisms were important to overcome therapeutic failure because of multidrug-resistance of cancer cells. SBCCC, with a lower IC50 compared to cisplatin, could render it the potential to overcome the side-effect for clinical application.
Highlights
Gastric cancer, as a multifactorial disorders, shows cytological and architectural heterogeneity compared to other gastrointestinal cancers, making it therapeutically challenging
When the logarithms of Schiff base copper coordinated compound (SBCCC) concentrations were plotted versus the inhibition rates, IC50 showed as 1 μM for both gastric cancer cell lines (Fig. 2a, right)
SBCCC induces cell death of gastric cancer cells To investigate the cellular events, apoptosis and cell growth arrest were determined by Flow cytometry
Summary
As a multifactorial disorders, shows cytological and architectural heterogeneity compared to other gastrointestinal cancers, making it therapeutically challenging. Schiff bases derived from an amino and carbonyl compound belong to an important class of ligands that coordinated to metal ions. Schiff base-metal compounds have been reported to have promising antibacterial and antitumor activities [6, 7], while the Schiff base coordinated with copper compounds shows the most prominent in the class of molecules [8,9,10,11,12,13]. The potential anticancer effects of Schiff base copper compounds are well reported in various cancer cell lines, including oxidative DNA cleavage to kill cancer stem cell-enriched cells (HMLER-shEcad) and bulk cancer cells (HMLER) [15], inducing apoptosis in lung (A-549) and breast (MDA-MB-231) human cancer cell lines [16], and inducing necrotic cell death and autophagy in breast
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