Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells

Abstract

Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 μM). Treatments induced apoptosis, increased BAX/BCL-2 ratio and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy.

Anti-proliferative and apoptotic effect of cannabinoids on human pancreatic ductal adenocarcinoma xenograft in BALB/c nude mice model

“…The consequence was an increased BAX/BCL-2 ratio in cannabinoid–treated groups. The increase in BAX/BCL-2 ratio reflected the critical confirmation of tumor cell death 36 – 38 . Similarly, a previous study demonstrated that CBD stimulated apoptosis via downregulation of protein BCL-2 and upregulation of protein BAX in gastric cancer cell lines 33 .…”

“…Remarkably, BAX/BCL–2 ratio has been widely accepted as a protein expression pattern to estimate the eventual outcome of apoptosis expression in cancer patients 36 – 38 . An imbalance of protein BAX and BCL-2 expression may associate with the activation of the apoptosis process in cancer cells 29 , 30 , 33 .…”

Coumarins as Fungal Metabolites with Potential Medicinal Properties

“…In addition, promising results were obtained by replacing the methoxyls at the 3 and 5 positions of the vinylbenzene moiety with methyl groups (–CH 3 ), as evidenced by the effects of the compound characterized by a submicromolar IC 50 value. The two just mentioned coumarin hybrids exhibited pharmacologically relevant antiproliferative activity and underwent deep biological investigations, thus revealing their ability to induce an appreciable level of apoptosis comparable to that of cisplatin, an extremely important but toxic drug [ 170 ].…”

Influence of acid–base equilibrium on interactions of some monofunctional coumarin Pd(ii) complexes with biologically relevant nucleophiles-comprehensive kinetic study

“…Furthermore, scientists directed their attention towards the synthesis of suitable organometallic complexes to enhance biological activity. Complexes of platinum( ii ), 10 palladium( ii ), 11,12 cerium( iii ), 13 zirconium( iv ), 14 copper( ii ), 15 zinc( ii ), 16 bismuth( iii ), 17 and cadmium( ii ) 18 containing coumarins as a ligand showed significant in vitro cytotoxic activity.…”