Abstract
The pancreatic cancer is the fourth leading cause of cancer-related death and characterized by one of the lowest five-year survival rate. The current therapeutic options are demonstrating minimal effectiveness, therefore studies on new potential anticancer compounds, with non-significant side effects are highly desirable. Recently, it was demonstrated that vanadium compounds, in particular organic derivatives, exhibit anticancer properties against different type of tumor as well as favorable biodistribution from a pancreatic cancer treatment perspective.In this research, we showed selective cytotoxic effect of vanadium complexes, containing phenanthroline and quinoline as an organic ligands, against human pancreatic ductal adenocarcinoma cell line (PANC-1), compared to non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE). Results exhibited that vanadium complexes inhibited autophagy process in selective cytotoxic concentration as well as caused the cell cycle arrest in G2/M phase associated with mitotic catastrophe and increased level of reactive oxygen species (ROS). Moreover, in higher concentration, vanadium derivatives induced a mix type of cell death in PANC-1 cells, including apoptotic and necroptotic process.Our investigation emphasizes the anticancer potential of vanadium complexes by indicating their selective cytotoxic activity, through different process posed by alternative type of cell deaths to apoptosis-resistant cancer cells. Further studies supporting the therapeutic potential of vanadium in pancreatic cancer treatment is highly recommended.
Highlights
IntroductionIn spite of the fact that pancreatic cancer is much less common than the breast or bowel tumor, it is characterized by one of the lowest 5-year survival rate
The pancreatic cancer is the fourth leading cause of cancer-related death
In the present study we have selected seven vanadium complexes (C1-Compound 7 (C7)), the structure shown in Figure 1, to evaluate their cytotoxicity against human pancreas ductal adenocarcinoma cells in vitro
Summary
In spite of the fact that pancreatic cancer is much less common than the breast or bowel tumor, it is characterized by one of the lowest 5-year survival rate. More than 80% of patients are identified with locally advanced and metastatic stage, unable to surgical resection. This is caused by delayed diagnosis and lack of specific urine or blood markers which could be used to identify patients with increased risk [5,6,7]. Even for the 20% patients with a resectable tumor, prospect of long-term survival is still unavailable. The incidence of pancreatic cancer is highly diverse across regions and populations, suggesting the influence of genetic and environmental factors. About 90% of pancreatic tumor is derived from the ductal epithelium of pancreas and termed as pancreatic ductal adenocarcinoma (PDAC) [1]
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