مائده دژم فکر

Gastric cancer is the fourth most common cancer worldwide and the second leading cause of death from cancer. In recent years, advances in cancer therapy have raised the specter of developing effective agents of high-impact diseases, like gastric cancer, which remains one of the major causes of cancer deaths in the world. Recently it has been demonstrated that vanadium compounds exhibit a wide variety of pharmacological properties in humans. Vanadium compounds show interesting biological and pharmacological properties and some of them display antitumoral actions. However, the mechanism of action of vanadium compounds in the inhibition of cancer cell proliferation is still elusive. In this study, the antioxidant properties of the vanadium compounds were evaluated by two in vitro tests: Ferric reducing ability of plasma (FRP) and 2,2-diphenyl-1-picryl-hydrate (DPPH) radical scavenging. The toxicity of vanadium compounds on cancer cells MKN45 (a gastric cancer cell line) was investigated by using the test MTT in various concentrations of 1, 10, 50, 100, and 500 μg/ml. The percentage of apoptotic cells, after these treatments were investigated using Acridine orange/ Ethidium bromide staining. Wound healing and morphological modification were performed in vitro to examine migration and adhesion in the gastric cancer cell line by invert microscopy. The assessments with DPPH and FRAP techniques showed that vanadium compounds have antioxidant activities. Data showed with an increasing concentration of vanadium compounds the percentage of remaining living cells of MKN45 significantly decreased (P˂0.05). All vanadium compounds showed considerable cytotoxic activity against cancer cell lines (IC50 = 1 μg/ml). The apoptosis investigations showed that vanadium compounds can induce high percentage of apoptosis in a dose of 1 μg/ml. The apoptotic inducing effect of vanadium compounds were confirmed by morphological observation. Migration studies revealed that vanadium compounds have inhibitory effect against the metastatic potency of MKN45 cancer cell lines. The results of this study showed that the vanadium compounds had high cytotoxic effect on gastric cancer cells (MKN45); and the percentage of lethality, with the passage of time and with increased concentration had risen.

Autophagy is a survival pathway required for cellular viability during starvation through catabolic self digestion of damaged proteins and organelles; however, autophagy may result in cell death if it proceeds to completion. Although the exact mechanism of this process is not clear, it seems that proper regulation of autophagy can potentially contribute to the therapeutics of cancers. The aim of this study was to determine the role of Arsenic trioxide (As2O3) in the induction of autophagy in human acute promyelocytic leukemia.

In this study, the role of autophagy in the As2O3-induced death of NB4 cells was assessed using electron microscopy. Also, quantitative real-time PCR method was used for expression of autophagy related genes in dose and Time dependent manner.

Our results showed that autophagy induces death in NB4 cells treated with arsenic trioxide. It was also found that the Atg7, Bclin1 and LC3 genes, which are essential genes for induction of autophagy, are the target of arsenic trioxide invasion.

This study showed As2O3-induced autophagy plays an important role in eliminating leukemia cells and treatment of cancer.