The prognosis for individuals dealing with uterine sarcomas and carcinosarcoma is typically unfavorable, highlighting the serious nature of these conditions. However, chemotherapy treatments tend to have many side effects and generally don’t help patients live longer. As a result, this blog will cover the study “Isobolographic Analysis Demonstrates the Additive and Synergistic Effects of Gemcitabine Combined with Fucoidan in Uterine Sarcomas and Carcinosarcoma Cells” by Marcin Bobiński et al. The study explored how the natural compound fucoidan (derived from Undaria pinnatifida) interacts with the chemotherapy drug gemcitabine, focusing on its antitumor effects, and it involved experiments on SK-UT-1, SK-UT1-B (carcinosarcoma), MES-SA (leiomyosarcoma), and ESS-1 (endometrial stromal sarcoma) cell lines.
Cells were incubated in the presence of gemcitabine, fucoidan, and the mixture, and MTT tests were performed after incubation. The interaction of the compounds was assessed using isobolographic analysis. The results obtained by isobolographic analysis are shown in Figures 1, 2, and 3, where the median inhibitory concentrations (IC50) of gemcitabine (GEM) and fucoidan (FUK) are plotted on the X-axis and Y-axis, respectively. Additive effects of gemcitabine and fucoidan combination treatment were observed in ESS-1 and SK-UT-1 cell lines. Synergistic effects were observed in SK-UT-1B cell line. Due to the MES-SA cell line’s poor response to the treatment, the relationship between fucoidan and gemcitabine couldn’t be established.
Appropriate concentrations of the mixtures for apoptosis evaluation were selected. For SK-UT-1 and SK-UT-1B, a concentration of 0.5 IC50 was used for both agents. A concentration of 0.05 IC50 was selected for the experiments because a very strong effect was observed in the ESS-1 cell line. The ESS-1 cell line showed the most significant apoptosis when treated with both gemcitabine and the gemcitabine-fucoidan combination. This effect was also observed in SK-UT-1B cells. Apoptosis induction in the SK-UT-1 cell line was very weak for both single agents and in combination. Although statistical significance was observed between single agents and in combination, the differences compared to the control were not significant.
The impact of combining gemcitabine and fucoidan on the SK-UT-1B cell line’s cell cycle arrest was contrasted with the effect of gemcitabine alone. Cell cycle analysis of cells treated with gemcitabine and fucoidan combinations. The most significant effect of gemcitabine and fucoidan combination therapy on cell cycle arrest (measured as the percentage of cells in pre-G1 and G0/G1 phases) was detected in the SK-UT-1 B cell line (compared to control and gemcitabine-treated groups). In the ESS-1 cell line, significant differences were observed between gemcitabine-treated and control cells, but no significant differences were observed between gemcitabine and combination treatment groups. Although certain phases displayed statistical significance, the differences in the number of cells within each cell cycle phase of SK-UT-1 cells, after exposure to the examined drugs, were quite small.
The research data indicated that combining fucoidan and gemcitabine had additive and even greater-than-additive effects on endometrial stromal sarcoma (ESS-1) and carcinosarcoma (SK-UT-1, SK-UT-1B) cell lines, proving fucoidan’s efficacy was better or equal to the combined effects of the individual treatments. The addition of fucoidan to gemcitabine enhances the apoptosis-inducing effect of gemcitabine in endometrial stromal sarcoma (ESS-1) but not in carcinosarcoma (SK-UT-1, SK-UT-1B) cell lines.
Gemcitabine alone doesn’t stop the cell cycle in carcinosarcoma (SK-UT-1, SK-UT-1B) cell lines. The addition of fucoidan to gemcitabine induces this effect in a carcinosarcoma tumor model (SK-UT-1B). The resistance of the MES-SA uterine leiomyosarcoma cell line to the combined drugs necessitates exploring different treatment plans to enhance the therapeutic outcome.
In light of these findings, the combination of gemcitabine and fucoidan is regarded as a potentially advantageous alternative therapeutic approach that may serve to increase the effectiveness and improve the safety aspects of medical treatments.
Source: Cancers (Basel) 2019 Dec 31;12(1):107. doi: 10.3390/cancers12010107.