Abstract

Pancreatic cancer, due to its asymptomatic development and drug-resistance, is difficult to cure. As many metallic and carbon-based nanomaterials have shown anticancer properties, we decided to investigate their potential use as anticancer agents against human pancreatic adenocarcinoma. The objective of the study was to evaluate the toxic properties of the following nanomaterials: silver (Ag), gold (Au), platinum (Pt), graphene oxide (GO), diamond (ND), and fullerenol (C60(OH)40) against the cell lines BxPC-3, AsPC-1, HFFF-2, and HS-5. The potential cytotoxic properties were evaluated by the assessment of the cell morphology, cell viability, and cell membrane damage. The cancer cell responses to GO and ND were analysed by determination of changes in the levels of 40 different pro-inflammatory proteins. Our studies revealed that the highest cytotoxicity was obtained after the ND treatment. Moreover, BxPC-3 cells were more sensitive to ND than AsPC-1 cells due to the ND-induced ROS production. Furthermore, in both of the cancer cell lines, ND caused an increased level of IL-8 and a decreased level of TIMP-2, whereas GO caused only decreased levels of TIMP-2 and ICAM-1 proteins. This work provides important data on the toxicity of various nanoparticles against pancreatic adenocarcinoma cell lines.

Highlights

  • Very often, pancreatic cancer is a silent killer that displays no symptoms until it is too late for effective therapy

  • As graphene oxide (GO) may induce oxidative stress in cancer cells, we suggest that epithelial-mesenchymal transition might be induced through the activation of the H2O2/ERK/NF-κB axis

  • The results indicate that more pronounced cytotoxic effects against certain human pancreatic cancer cell lines were achieved after carbon-based NP treatment rather than metallic NPs

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Summary

Introduction

Pancreatic cancer is a silent killer that displays no symptoms until it is too late for effective therapy. It is estimated that around 73% of patients will die within the first year after diagnosis [1], and that only 15% of patients will have a chance to qualify to undergo surgery, which is the most promising anticancer therapy to date [2]. For these reasons, pancreatic cancer, which is the 11th most common type of cancer and the 7th leading cancer-related cause of death worldwide, remains a worldwide public health issue [3]. Few of the commercially available pancreatic adenocarcinoma cell lines are characterized by resistance to the pyrimidine nucleoside analogue gemcitabine, which is still one of the most important agents that is used in treatment, including BxPC-3 [5] and AsPC-1 [6]

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