Paweł Stączek

Biological Activity of fac-[Re(CO)3(phen)(aspirin)], fac-[Re(CO)3(phen)(indomethacin)] and Their Original Counterparts against Ishikawa and HEC-1A Endometrial Cancer Cells

Nonsteroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase enzyme (COX) and were found to have positive effects in reducing the risk of developing gynecological cancers. However, long-term administration of NSAIDs carries the risk of various side effects, including those in the digestive and circulatory systems. Therefore, there is a constant need to develop new NSAID derivatives. In this work, we investigated rhenium NSAIDs, comparing their effects on endometrial cancer cells with original NSAIDs, demonstrating the high activity of aspirin and indomethacin derivatives. The cytotoxic activity of rhenium derivatives against the Ishikawa and HEC-1A cancer cell lines was higher than that of the original NSAIDs. The IC50 after 24-h incubation of Ishikawa and HEC-1A were 188.06 µM and 394.06 µM for rhenium aspirin and 228.6 µM and 1459.3 µM for rhenium indomethacin, respectively. At the same time, IC50 of aspirin and indomethacin were 10,024.42 µM and 3295.3 µM for Ishikawa, and 27,255.8 µM and 5489.3 µM for HEC-1A, respectively. Moreover, these derivatives were found to inhibit the proliferation of both cell lines in a time- and state-dependent manner. The Ishikawa cell proliferation was strongly inhibited by rhenium aspirin and rhenium indomethacin after 72-h incubation (*** = p < 0.001), while the HEC-1A proliferation was inhibited by the same agents already after 24-h incubation (*** = p < 0.001). Furthermore, the ROS level in the mitochondria of the tested cells generated in the presence of rhenium derivatives was higher than the original NSAIDs. That was associated with rhenium indomethacin exclusively, which had a significant effect (*** = p < 0.001) on both Ishikawa and HEC-1A cancer cells. Rhenium aspirin had a significant effect (*** = p < 0.001) on the mitochondrial ROS level of Ishikawa cells only. Overall, the research revealed a high potential of the rhenium derivatives of aspirin and indomethacin against endometrial cancer cells compared with the original NSAIDs.

Prospects of NSAIDs administration as double-edged agents against endometrial cancer and pathological species of the uterine microbiome

Many types of cancers, including endometrial cancer, were found to have cyclooxygenase-2 (COX-2) overexpression. Because this enzyme belongs to the group of pro-inflammatory enzymes, so-called NSAIDs (non-steroidal anti-inflammatory drugs) directly inhibit its activity. An increasing number of reports on COX-2 involvement in cancer, as well as on the role of microbiota in abnormal metabolism and signaling of cells, forces the development of new NSAID types. Besides, NSAIDs can affect some bacteria, which are vaginal/endometrial microbiome members. The overgrowth of those species was found to be a major cause of some uterus diseases. Those infections can lead to chronic inflammatory response and suppress anti-tumorigenic cell pathways. The purpose of this review is to highlight the COX-2 enzyme role in endometrial cancer, the potential effect of the endometrial microbiome on COX-2 enzyme overexpression, and the prospects of NSAIDs use in terms of this type of cancer.