The Effect of α-Mangostin and Cisplatin on Ovarian Cancer Cells and the Microenvironment

Abstract

Ovarian cancer is one of the cancers that, unfortunately, is detected at a late stage of development. The current use of treatment has many side effects. Notably, up to 20% of patients show cisplatin resistance. We assess the effects of cisplatin and/or α-mangostin, a natural plant derivative, on ovarian cancer cells and on the cancer cell microenvironment. The effect of cisplatin and/or α-mangostin on the following cells of ovarian cancer lines: A2780, TOV-21G, and SKOV-3 was verified using the XTT cytotoxicity assay. The separate and combined effects of tested drugs on ovarian cancer cell viability were assessed. We assessed the influence of chemotherapeutic agents on the possibility of modulating the microenvironment. For this purpose, we isolated exosomes from drug-treated and untreated ovarian cancer cells. We estimated the differences in the amounts of exosomes released from cancer cells (NTA technique). We also examined the effects of isolated exosome fractions on normal human cells (NHDF human fibroblast line). In the present study, we demonstrate that treatment of A2780, SKOV-3, and TOV-21G cells with α-mangostin in combination with cisplatin can allow a reduction in cisplatin concentration while maintaining the same cytotoxic effect. Ovarian cancer cells release a variable number of exosomes into the microenvironment when exposed to α-mangostin and/or cisplatin. However, it is important to note that the cargo carried by exosomes released from drug-treated cells may be significantly different.

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

“…The exosomes were then isolated from untreated and drug-treated SKOV-3 and TOV-21G cells. The quantitative and qualitative analysis of the results was presented in the publication [ 18 ].…”

“…It is possible to achieve the same cytotoxic effect for a drug combination with a lower concentration of cisplatin as compared to the use of cisplatin alone. These results give hope that the reduction in the concentration of cisplatin in combination with α-mangostin will be associated with a reduction in numerous side effects in relation to the currently used cisplatin alone [ 18 , 21 , 22 ]. The use of new drugs in the treatment of cancer may be more than just reducing the side effects of chemotherapy.…”

“…Our studies to date have shown that treatment of SKOV-3 and TOV-21G cells with α-mangostin and/or cisplatin leads to changes in the number of exosomes released. We also showed that these exosomes, depending on the origin and treatment conditions, show different activity against normal fibroblasts [ 18 ]. In this study, we attempted to assess the change in the expression of genes involved in metastasis in normal fibroblasts under the influence of neoplastic exosomes.…”

“…The cytotoxicity of the compounds was assessed using the XTT test by determining the IC50 value (half maximal inhibitory concentration). To determine the optimal concentration of drug combinations (α-mangostin and cisplatin), the XTT test was performed, followed by the analysis using the CompuSyn software (ComboSyn, Inc., New York, NY, USA) [ 18 , 85 , 86 ]. The results of the performed analyzes and the determined concentrations for the subsequent stages of the research are summarized in Table 3 [ 18 ].…”

“…Modulation of the neoplastic microenvironment through various drug combinations can significantly influence the development of metastases. We have noted that ovarian cancer cells of different stages secrete different numbers of exosomes depending on the treatment conditions [ 18 ]. It can be assumed that the cargo carried by such exosomes also varies.…”