Piotr Paduszyński

Current Research on the Control Mechanisms of Cell Survival and Proliferation as Potential Interaction Sites with Pentacyclic Triterpenoids in Ovarian Cancer

The treatment of gynecological cancers is challenging because they are often diagnosed at the advanced stages. Furthermore, available chemotherapeutics increasingly imply the development of resistance in cancer patients. This necessitates the search for alternative solutions that could be used in therapy. One of the possibilities to consider is the use of pentacyclic triterpenoids. They are naturally occurring compounds characterized by a wide range of biological activities. They can also be modified to improve their pharmacological properties. Terpenoids based on oleanane, ursane, and lupane skeletons can modulate the numerous processes occurring in both normal and transformed cells. To develop effective anti-cancer therapy, it is essential to understand the processes regulating the progression and suppression of a given type of cancer. For this reason, it is necessary to assess the influence of the tested compounds on cellular processes such as the cell cycle, epithelial–mesenchymal transition, autophagy, and apoptosis. This article summarizes available information on the effects of pentacyclic triterpenoids on the PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Notch, HIF-1α, TGF-β, Wnt/β-catenin, Hippo, and Hedgehog signaling pathways in ovarian cancer cells.

Antiproliferative and Cytotoxic Properties of Propynoyl Betulin Derivatives against Human Ovarian Cancer Cells: In Vitro Studies

Due to the incidence of ovarian cancer (OC) and the limitations of available therapeutic strategies, it is necessary to search for novel therapeutic solutions. The aim of this study was to evaluate the cytotoxic effect of betulin 1 and its propynoyl derivatives 2–6 against ovarian cancer cells (SK-OV-3, OVCAR-3) and normal myofibroblasts (18Co). Paclitaxel was used as the reference compound. The propynoyl derivatives 2–6 exhibited stronger antiproliferative and cytotoxic activities compared to betulin 1. In both ovarian cancer cell lines, the most potent compound was 28-propynoylbetulin 2. In the case of compound 2, the calculated IC50 values were 0.2 µM for the SK-OV-3 cells and 0.19 µM for the OVCAR-3 cells. Under the same culture conditions, the calculated IC50 values for compound 6 were 0.26 µM and 0.59 µM, respectively. It was observed that cells treated with compounds 2 and 6 caused a decrease in the potential of the mitochondrial membrane and a significant change in cell morphology. Betulin 1, a diol from the group of pentacyclic triterpenes, has a confirmed wide spectrum of biological effects, including a significant anticancer effect. It is characterized by low bioavailability, which can be improved by introducing changes to its structure. The results showed that chemical modifications of betulin 1 only at position C-28 with the propynoyl group (compound 2) and additionally at position C-3 with the phosphate group (compound 3) or at C-29 with the phosphonate group (compound 6) allowed us to obtain compounds with greater cytotoxic activity than their parent compounds, which could be used to develop novel therapeutic systems effective in the treatment of ovarian cancer.