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Abstract
Pancreatic cancers are among of the most lethal types of neoplasms, and are mostly detected at an advanced stage. Conventional treatment methods such as chemotherapy or radiotherapy often do not bring the desired therapeutic effects. For this reason, natural compounds are increasingly being used as adjuvants in cancer therapy. Polyphenolic compounds, including resveratrol, are of particular interest. The aim of this study is to analyze the antiproliferative and pro-apoptotic mechanisms of resveratrol on human pancreatic cells. The study was carried out on three human pancreatic cancer cell lines: EPP85-181P, EPP85-181RNOV (mitoxantrone-resistant cells) and AsPC-1, as well as the normal pancreatic cell line H6c7. The cytotoxicity of resveratrol in the tested cell lines was assessed by the colorimetric method (MTT) and the flow cytometry method. Three selected concentrations of the compound (25, 50 and 100 µM) were tested in the experiments during a 48-h incubation. TUNEL and Comet assays, flow cytometry, immunocytochemistry, confocal microscopy, real-time PCR and Western Blot analyses were used to evaluate the pleiotropic effect of resveratrol. The results indicate that resveratrol is likely to be anticarcinogenic by inhibiting human pancreatic cancer cell proliferation. In addition, it affects the levels of Bcl-2 pro- and anti-apoptotic proteins. However, it should be emphasized that the activity of resveratrol was specific for each of the tested cell lines, and the most statistically significant changes were observed in the mitoxantrone-resistant cells.
Highlights
Despite developments in the field of early cancer detection, the number of new cases is increasing at an alarming rate [1]
It was observed that the exposure of pancreatic cell lines to resveratrol inhibited proliferation in a concentrationand time-dependent manner compared to untreated cells (Figure 2A–D)
The results of our research show the antitumor potential of resveratrol in terms of antiproliferative and pro-apoptotic effects on human pancreatic cells by changing the expression of proteins related to the apoptotic process
Summary
Despite developments in the field of early cancer detection, the number of new cases is increasing at an alarming rate [1]. Pancreatic cancers, classified as one of the most aggressive malignant neoplasms in humans, pose a particular problem [2,3,4]. Cancer treatment focuses mainly on surgery, radiotherapy, and chemotherapy, depending on the type and severity of the disease at the time of diagnosis. In the case of pancreatic cancer, surgery is the most effective treatment [5]. Due to the diagnosis of this disease in its late stage of development, only 15–20% of patients qualify for surgical removal of the tumor [6]. At the time of diagnosis, the vast majority of patients have numerous metastases, disqualifying them from surgery [5,6]. The use of chemotherapeutic agents has led to the development of acquired multidrug resistance [7,8]
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