Biology subjects

Katsoris, P.

Publications and source records attributed to Katsoris, P..

4 recordsLinked to original sources

bioRxiv2024

Poly-unsaturated Fatty Acids from Thamnidium elegans and Mortierella alpina Suppress Prostate Cancer Cells Proliferation and Migration

Thamnidium elegans and Mortierella alpina are two oleaginous fungi that belong to Mucoromycota that synthesize polyunsaturated fatty acids which are credited with multiple health benefits and possible anticancer properties. These fungi were cultivated on culture media with glucose or glycerol as a carbon source. After extracting the lipids, we transformed them into fatty acid lithium salts (FALS), which are water-soluble and absorbable mammalian cells, including DU-145 and PC-3 cancer cells. The two cell lines, both long-established prostate cancer models, were treated with FALS and indicated increased susceptibility to the lipid derivatives. The viability and proliferation rates were significantly reduced, as well as their migratory capabilities, which were significantly impaired compared to olive-oil-derived FALS, which were used as a control substance. We conclude that the FALS derivatives of microbial lipids from these organisms exhibit anticancer effects by suppressing the proliferation and migration of human prostate cancer cell lines.

cancer biology↗

bioRxiv2024

The ERK1/2-Elk1, JNK-cJun, and JAK-STAT Transcriptional Axes as Potential Bortezomib Resistance Mediators in Prostate Cancer

The effectiveness of proteasome inhibitors against solid tumors is limited as the emergence of resistance is rapid. Although many mechanisms have been proposed and verified, no definite answer has been given, highlighting the complexity of the resistant phenotype. In this study, a Bortezomib-resistant prostate cancer cell line is created, and a broad-spectrum signaling pathway analysis is performed to identify differences and adaptations the resistant cells exhibit. Our findings highlight the upregulation and activation of Nf-{kappa}B, STAT3, cJun, and Elk1 transcription factors in the resistant cells and the subsequent evasion of apoptosis and induction of autophagy, which is constantly activated and substitutes the role of the ubiquitin-proteasome system (UPS). Additionally, assessment of the intracellular reactive oxygen species in resistant cells confirms their downregulation, which is theorized to be a consequence of metabolic changes, increased autophagic flux, and antioxidative enzyme action. The results of this study highlight the potential therapeutic targeting of key kinases and transcription factors, participating in the main signaling pathways and gene regulation of Bortezomib-resistant cells, that could re-sensitize the cells to proteasome inhibitors, thus surpassing the current limitations.

cancer biology↗

bioRxiv2024

Human Recombinant Thyrotropin Fails to Induce Thyroid Cell Proliferation

Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores for the first time the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of PTC patients.

cancer biology↗

bioRxiv2023

Investigating the mechanisms underlying Bortezomib resistance

Proteasome inhibitors such as Bortezomib, represent an established type of targeted treatment for several types of hematological malignancies, including multiple myeloma, Waldenstroms macroglobulinemia and mantle cell lymphoma, based on the cancer cells susceptibility upon impairment of the proteasome-ubiquitin system. However, a major problem limiting their efficacy is the emergence of resistance. Their application on solid tumors is currently being studied, while simultaneously, a wide spectrum of hematological cancers, such as Myelodysplastic Syndromes show minimal or no response to Bortezomib treatment. In this study, we utilize the prostate cancer cell line DU-145 to establish a model of Bortezomib resistance, studying the underlying mechanisms. Evaluating the resulting resistant cell line, we observed restoration of proteasome chymotrypsin-like activity, regardless of drug presence, an induction of pro-survival pathways, and the substitution of the Ubiquitin-Proteasome System role in proteostasis by induction of autophagy. Finally, an estimation of the oxidative condition of the cells, indicated that the resistant clones reduce the generation of reactive oxygen species induced by Bortezomib, to levels even lower than those induced in non-resistant cells. Our findings elucidate key proteins of survival and stress regulation pathways as potential pharmaceutical targets, which could increase the efficiency of the proteasome-targeting therapies, thus expanding the group of molecular targets for neoplastic disorders.

cancer biology↗