Ilona Anna Bednarek

Hyperthermia Potentiates the Effectiveness of Anticancer Drugs—Cisplatin and Tamoxifen on Ovarian Cancer Cells In Vitro

Ovarian cancer is one of the most prevalent cancers among women. Due to the frequent problems during treatment, such as relapses or the development of resistance to treatment, new methods of treating this disease are being sought. A special attention is directed towards the combination therapies combining several different anticancer agents. The aim of the following study was to examine the effect of combination therapy with mild hyperthermia (temperatures of 39 °C and 40 °C) and anticancer drugs—cisplatin and tamoxifen—on the SKOV-3 ovarian cancer cell line in vitro. Furthermore, the study also assessed the effect of moderate hyperthermia on the anticancer effectiveness of both of these drugs. The cytotoxic effect of the therapy was assessed using MTT assay and fluorescent acridine orange staining. Changes in the expression of genes involved in apoptosis processes were evaluated using RT-qPCR. It has been shown that the use of combination therapy leads to a significant increase in apoptosis processes in SKOV-3 ovarian cancer cells and, consequently, to a decrease in their viability. At the molecular level, mild hyperthermia leads primarily to a decrease in the expression of anti-apoptotic genes, and also, to a small extent, to an increase in the expression of proapoptotic genes. The results also indicate that moderate hyperthermia has a positive effect on the cytotoxic efficacy of both cisplatin and tamoxifen on ovarian cancer cells. This suggests that hyperthermia could be a potential component in combination therapy for ovarian cancer.

Cisplatin in Ovarian Cancer Treatment—Known Limitations in Therapy Force New Solutions

Cisplatin is one of the most commonly used anticancer drugs worldwide. It is mainly used in the treatment of ovarian cancer, but also used in testicular, bladder and lung cancers. The significant advantage of this drug is the multidirectional mechanism of its anticancer action, with the most important direction being damaging the DNA of cancer cells. Unfortunately, cisplatin displays a number of serious disadvantages, including toxicity to the most important organs, such as kidneys, heart, liver and inner ear. Moreover, a significant problem among patients with ovarian cancer, treated with cisplatin, is the development of numerous resistance mechanisms during therapy, including changes in the processes of cellular drug import and export, changes in the DNA damage repair mechanisms, as well as numerous changes in the processes of apoptosis and autophagy. Due to all of the mentioned problems, strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer are intensively sought. The most important strategy includes the development of less toxic cisplatin analogs. Another important direction is combination therapy, involving the simultaneous use of cisplatin with different anticancer drugs, substances derived from plants, temperature or radiotherapy. Many years of observations accompanying the presence of cisplatin in the therapy made it possible to provide a series of verifiable, statistically significant data, but also to show how, over time, with the new information and scientific discoveries, it is possible to describe and understand the therapeutic problems observed in practice, such as the acquisition of drug resistance by tumor cells or induction of changes in the tumor microenvironment. According to the authors, confronting what we knew so far with what new trends offer has a profound meaning. This paper presents information on the history of cisplatin and describes the molecular mechanisms of its action and the development of resistance by cancer cells. In addition, our goal was to highlight a number of therapeutic strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer, as well as to identify methods to eliminate problems associated with the use of cisplatin.

Morin exerts anti-metastatic, anti-proliferative and anti-adhesive effect in ovarian cancer cells: an in vitro studies

AbstractThe influence of morin hydrate on changes of proliferative, metastatic, and adhesive potential of human ovarian cancer cells concerning the influence of decitabine, and decitabine with trichostatin A, and in comparison to untreated cells, were analyzed. The effect of morin hydrate, decitabine, and trichostatin A were examined in A2780 and SKOV-3 ovarian cancer cell lines using MTS assay, clonogenic assay, adhesion to endothelial HMEC-1 cells, transwell migration assay and cell cycle analysis. The expression level of epithelial to mesenchymal transition (EMT) markers was quantified using PCR Array in relation to the level of global methylation determined with Methylated DNA Quantification Kit. We observed statistically significant inhibition of adhesive and migratory potential of both cell lines and the accumulation of G0/G1 phase A2780 cells after treatment with morin hydrate. Our studies confirmed the influence of morin hydrate on down-regulation of genes considered as up-regulated during EMT, and up-regulation of some genes considered as down-regulated during EMT in A2780 and SKOV-3 cells. Phenotypic changes were associated with molecular changes in cells, eg. decrease of the expression level of genes associated with adhesion, and an increase of genes down-regulated during EMT, after morin hydrate treatment in comparison to untreated control cells in both cell lines, were observed.

Alpha Mangostin and Cisplatin as Modulators of Exosomal Interaction of Ovarian Cancer Cell with Fibroblasts

The diversity of exosomes and their role in the microenvironment make them an important point of interest in the development of cancer. In our study, we evaluated the effect of exosomes derived from ovarian cancer cells on gene expression in fibroblasts, including genes involved in metastasis. We also attempted to evaluate the indirect effect of cisplatin and/or α-mangostin on metastasis. In this aspect, we verified the changes induced by the drugs we tested on vesicular transfer associated with the release of exosomes by cells. We isolated exosomes from ovarian cancer cells treated and untreated with drugs, and then normal human fibroblasts were treated with the isolated exosomes. Changes in the expression of genes involved in the metastasis process were then examined. In our study, we observed altered expression of genes involved in various steps of the metastasis process (including genes related to cell adhesion, genes related to the interaction with the extracellular matrix, the cell cycle, cell growth and proliferation, and apoptosis). We have shown that α-mangostin and/or cisplatin, as chemotherapeutic agents, not only directly affect tumor cells but may also indirectly (via exosomes) contribute to delaying metastasis development.