MFE-280

MSM Decreases Viability of EC Cells in a Dose-Dependent Manner

Methylsulfonylmethane (MSM) is an over-the-counter dietary supplement with anti-inflammatory, antioxidative, and osteoarthritis, gastric injury, obesity-associated disorders, and other conditions ameliorating properties. Multiple research studies have demonstrated that MSM holds therapeutic potential for treating various cancer types such as endometrial cancer (EC). In this study, Kowalska et al. used EC cell lines (ISHIKAWA, MFE-296, and MFE-280) to determine the effects of MSM, either alone or in combination with the chemotherapy drug doxorubicin (DOX).

Firstly, they evaluated the effect of MSM on EC cells and observed that MSM decreases the viability of EC cells in a dose-dependent manner (Fig. 1a). ISHIKAWA cell line, which represents the well differentiated EC, presented the highest sensitivity to MSM as compared to moderately differentiated MFE-296 and poorly differentiated MFE-280. A significant decrease in the viability of ISHIKAWA and MFE-296 cell lines was observed for doses of MSM below 600 mM. MFE-280 cells demonstrated a significant response at 300 mM and higher doses. For the rest of experiments, the concentrations of 300 mM and 400 mM of MSM were chosen. Both doses of MSM are for most of the cell lines above the IC₅₀: for ISHIKAWA IC₅₀ = 538.6 mM, MFE-296 IC₅₀ = 551.1 mM MSM, and for MFE-280 IC₅₀ = 380 mM MSM, based on AlamarBlue assay results.

Fig. 1. Methylsulfonylmethane sensitizes endometrial cancer cells to doxorubicin (Kowalska K, Habrowska-Górczyńska D E, et al., 2021).

Fuling Overrides the Estradiol-Mediated Potentiation of Endometrial Cancer Cell Lines Invasiveness

The Traditional Chinese medicine, Guizhi Fuling (here called Fuling), has been confirmed in meta-analysis studies to reduce recurrence of endometriosis and improve pregnancy outcomes; however, the possible use of Fuling as a fertility-preserving treatment in endometrial cancer has not previously been tested. Khan et al. explored this by testing Fuling on two endometrial cancer cell lines (Ishikawa and MFE-280).

The extract of Fuling inhibited the invasiveness of both cell lines in a dose-dependent manner. The invasiveness of cells was assessed using transwell assays after 24 hours (Fig. 2). Box plots show that Fuling decreased invasiveness by 50% at around 58 µg/ml for Ishikawa and 52 µg/ml for MFE-280 (Fig. 2A and B). Representative invasion images are presented in Figure 2C. In order to evaluate its effects on 2D surface migration, a wound was scratched in confluent cell monolayers. After 24 hours of incubation with 80 µg/ml of Fuling or vehicle (DMSO), wound closure was calculated with NIH-Image software. Fuling significantly reduced migration in both cell lines when compared to control (Fig. 3). The images of wound closure are shown in Figure 3A, B, and percent closure was calculated by normalizing to wound area before treatment (Fig. 3C).

Fig. 2. Dose-dependent inhibition of invasion of Ishikawa and MFE-280 cells by Fuling (Khan S, Varricchio A, et al., 2022).

Fig. 3. Decreased motility measured by reduced wound closure rates in plated Ishikawa and MFE-280 in cultures treated with 80 µg/ml Fuling, as compared with vehicle control (Khan S, Varricchio A, et al., 2022).