In Vitro Effects of Mitochondria-Targeted Antioxidants in a Small-Cell Carcinoma of the Ovary of Hypercalcemic Type and in Type 1 and Type 2 Endometrial Cancer

Abstract

Small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT) and endometrial cancer from type 1 and type 2 are gynecological tumors that affect women worldwide. The treatment encompasses the use of cytotoxic drugs that are nonspecific and inefficient. “Mitocans,” a family of drugs that specifically target tumor cells’ mitochondria, might be a solution, as they conjugate compounds, such as antioxidants, with carriers, such as lipophilic cations, that direct them to the mitochondria. In this study, caffeic acid was conjugated with triphenylphosphonium (TPP), 4-picolinium, or isoquinolinium, forming 3 new compounds (Mito6_TPP, Mito6_picol., and Mito6_isoq.) that were tested on ovarian (COV434) and endometrial (Hec50co and Ishikawa) cancer cells. The results of MTT and neutral red assays suggested a time- and concentration-dependent decrease in cell viability in all tumor cell lines. The presence of apoptosis was indicated by the Giemsa and Höechst staining and by the decrease in mitochondrial membrane potential. The measurement of intracellular reactive oxygen species demonstrated the antioxidant properties of these compounds, which might be related to cell death. Generally, Mito6_TPP was more active at lower concentrations than Mito6_picol. or Mito6_isoq., but was accompanied by more cytotoxic effects, as shown by the lactate dehydrogenase release. Non-tumorous cells (HFF-1) showed no changes after treatment. This study assessed the potential of these compounds as anticancer agents, although further investigation is needed.

The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells

“…After 72 h of interaction between CMs obtained from culture of M0, M1 and M2 macrophages, morphological abnormalities in hGCs and COV434 cells were evaluated by Giemsa stain [ 19 ]. hGCs and COV434 cells were seeded in a 24-well plate with round coverslips at densities of 7.0 × 10 5 and 3.5 × 10 5 cells/well, respectively.…”

“…After 24 h, the medium was removed, CMs obtained from culture of M0, M1 and M2 Martins et al Reproductive Biology and Endocrinology (2022) 20:116 macrophages were added to a final volume of 200 μL, and incubated for 72 h at 37 °C with 5% CO 2 atmosphere. MTT assay conditions were adapted from the work by Castelôa et al [19]. Briefly, at the end of incubation time, an MTT solution was added (0.5 mg/mL) and the plate was incubated for another 3 h at 37ºC with 5% CO 2 atmosphere.…”