Anna Paszel-Jaworska

Methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL), a synthetic oleanolic acid derivative, induces both apoptosis and autophagy in MDA-MB-231 breast cancer cells.

HIMOXOL (methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate) is a synthetic derivative of oleanolic acid (OA). HIMOXOL revealed the highest cytotoxic effect among tested synthetic OA analogs. In this study we focused on elucidating the cytotoxic mechanism of HIMOXOL in MDA-MB-231 breast cancer cells. HIMOXOL reduced MDA-MB-231 cell viability with an IC50 value of 21.08±0.24μM. In contrast to OA, the tested compound induced cell death by activating apoptosis and the autophagy pathways. More specifically, we found that HIMOXOL was able to activate the extrinsic apoptotic pathway, which was proven by observation of caspase-8, caspase-3 and PARP-1 protein activation in Western blot analysis. An increase in the ratio of Bax/Bcl-2 protein levels was also detected. Moreover, HIMOXOL triggered microtubule-associated protein LC3-II expression and upregulated beclin 1. This observed compound activity was modulated by mitogen-activated protein kinases and NFκB/p53 signaling pathways. Together, these data suggest that HIMOXOL, a synthetic oleanolic acid derivative which activates dual cell death machineries, could be a potential and novel chemotherapeutic agent.

Nanoscale size effect in in situ titanium based composites with cell viability and cytocompatibility studies

Novel in situ Metal Matrix Nanocomposite (MMNC) materials based on titanium and boron, revealed their new properties in the nanoscale range. In situ nanocomposites, obtained through mechanical alloying and traditional powder metallurgy compaction and sintering, show obvious differences to their microstructural analogue. A unique microstructure connected with good mechanical properties reliant on the processing conditions favour the nanoscale range of results of the Ti-TiB in situ MMNC example. The data summarised in this work, support and extend the knowledge boundaries of the nanoscale size effect that influence not only the mechanical properties but also the studies on the cell viability and cytocompatibility. Prepared in the same bulk, in situ MMNC, based on titanium and boron, could be considered as a possible candidate for dental implants and other medical applications. The observed relations and research conclusions are transferable to the in situ MMNC material group. Aside from all the discussed relations, the increasing share of these composites in the ever-growing material markets, heavily depends on the attractiveness and a possible wider application of these composites as well as their operational simplicity presented in this work.

Telomerase and drug resistance in cancer

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.

Proapoptotic activity and ABCC1-related multidrug resistance reduction ability of semisynthetic oleanolic acid derivatives DIOXOL and HIMOXOL in human acute promyelocytic leukemia cells.

One of the main problems of present-day oncology is the ability of neoplastic cells to develop different mechanisms of resistance to chemotherapeutic agent. A natural compound oleanolic acid (OA) was found to be active against many types of neoplastic cells. This paper examines the influence of eight semisynthetic oleanolic acid derivatives on drug-sensitive human acute promyelocytic leukemia cell line HL-60 and its multidrug resistant subline ABCC1 overexpressing HL-60/AR. Viability inhibition, proapoptotic activity, as well as influence on the ABCC1 gene expression level, ability to inhibit the transport function of multidrug resistance associated protein 1 (ABCC1) and to alter its level by the tested compounds, were evaluated. The most potent compounds were DIOXOL (methyl 3,11-dioxoolean-12-en-28-oate) and HIMOXOL (methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate). DIOXOL was most efficient in inducing apoptosis of HL-60 cells. It activated both intrinsic and extrinsic pathways of apoptotic cell death. Proapoptotic properties of DIOXOL were probably related to the significant decrease of p65 NFκB level and inhibition of its translocation to the nucleus. In turn, HIMOXOL was the most potent compound against resistant HL-60/AR cells. It inhibited ABCC1 transport function (short time response) and decreased the level of ABCC1 protein (long time response) as a result of reduction of ABCC1 expression.

In vitro biocompatibility of titanium after plasma surface alloying with boron.

Recently, the effect of different sizes of precursor powders during surface plasma alloying modification on the properties of titanium surface was studied. In this work we show in vitro test results of the titanium (α-Ti) after plasma surface alloying with boron (B). Ti-B nanopowders with 2 and 10wt% B were deposited onto microcrystalline Ti substrate. The in vitro cytocompatibility of these biomaterials was evaluated and compared with a conventional microcrystalline Ti. During the studies, established cell line of human gingival fibroblasts and osteoblasts were cultured in the presence of tested materials, and its survival rate and proliferation activity were examined. For this purpose, MTT assay, flow cytometric and fluorescent microscopic evaluation were made. Biocompatibility tests carried out indicate that the Ti after plasma surface alloying with B could be a possible candidate for dental implants and other medicinal applications. Plasma alloying is a promising method for improving the properties of titanium, thus increasing the field of its applications.