Browsing by Author "Górska-Ponikowska, Magdalena"

Now showing 1 - 4 of 4

Open Access
2-Methoxyestradiol and hydrogen peroxide as promising biomarkers in Parkinson’s disease
(2023) Bastian, Paulina; Konieczna, Lucyna; Dulski, Jarosław; Daca, Agnieszka; Jacewicz, Dagmara; Płoska, Agata; Knap, Narcyz; Sławek, Jarosław; Bączek, Tomasz; Kalinowski, Leszek; Drzeżdżon, Joanna; Roszmann, Anna; Belka, Mariusz; Górska-Ponikowska, Magdalena
Estrogens function in numerous physiological processes including controlling brain cell growth and differentiation. 2-Methoxestradiol (2-ME2), a 17β-estradiol (E2) metabolite, is known for its anticancer effects as observed both in vivo and in vitro. 2-ME2 affects all actively dividing cells, including neurons. The study aimed to determine whether 2-ME2 is a potentially cancer-protective or rather neurodegenerative agent in a specific tissue culture model as well as a clinical setup. In this study, 2-ME2 activity was determined in a Parkinson’s disease (PD) in vitro model based on the neuroblastoma SH-SY5Y cell line. The obtained results suggest that 2-ME2 generates nitro-oxidative stress and controls heat shock proteins (HSP), resulting in DNA strand breakage and apoptosis. On the one hand, it may affect intensely dividing cells preventing cancer development; however, on the other hand, this kind of activity within the central nervous system may promote neurodegenerative diseases like PD. Thus, the translational value of 2-ME2’s neurotoxic activity in a PD in vitro model was also investigated. LC-MS/MS technique was used to evaluate estrogens and their derivatives, namely, hydroxy and methoxyestrogens, in PD patients’ blood, whereas the stopped-flow method was used to assess hydrogen peroxide (H2O2) levels. Methoxyestrogens and H2O2 levels were increased in patients’ blood as compared to control subjects, but hydoxyestrogens were simultaneously decreased. From the above, we suggest that the determination of plasma levels of methoxyestrogens and H2O2 may be a novel PD biomarker. The presented research is the subject of the pending patent application “The use of hydrogen peroxide and 17β-estradiol and its metabolites as biomarkers in the diagnosis of neurodegenerative diseases,” no. P.441360.
Open Access
Curcumin and its new derivatives : correlation between cytotoxicity against breast cancer cell lines, degradation of PTP1B phosphatase and ROS generation
(2021-09-26) Kostrzewa, Tomasz; Wołosewicz, Karol; Jamrozik, Marek; Drzeżdżon, Joanna; Siemińska, Julia; Jacewicz, Dagmara; Górska-Ponikowska, Magdalena; Kołaczkowski, Marcin; Łaźny, Ryszard; Kuban-Jankowska, Alicja
Breast cancer is the most common cancer of women-it affects more than 2 million women worldwide. PTP1B phosphatase can be one of the possible targets for new drugs in breast cancer therapy. In this paper, we present new curcumin derivatives featuring a 4-piperidone ring as PTP1B inhibitors and ROS inducers. We performed cytotoxicity analysis for twelve curcumin derivatives against breast cancer MCF-7 and MDA-MB-231 cell lines and the human keratinocyte HaCaT cell line. Furthermore, because curcumin is a known antioxidant, we assessed antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the potential binding mode of new inhibitors within the allosteric site of the enzyme. We observed that two tested compounds are better anticancer agents than curcumin. Moreover, we suggest that blocking the -OH group in phenolic compounds causes an increase in the cytotoxicity effect, even at a low concentration. Furthermore, due to this modification, a higher level of ROS is induced, which correlates with a lower level of PTP1B.
Open Access
Skin and scalp under exposure to high-energy visible light : the current perspective
(2025) Jakubczyk-Słabicka, Anna; Kostrzewa, Tomasz; Barańska-Rybak, Wioletta; Górska-Ponikowska, Magdalena
Open Access
Synthesis, in vitro, and computational studies of PTP1B phosphatase inhibitors based on oxovanadium(IV) and dioxovanadium(V) complexes
(2022) Kostrzewa, Tomasz; Jończyk, Jakub; Drzeżdżon, Joanna; Jacewicz, Dagmara; Górska-Ponikowska, Magdalena; Kołaczkowski, Marcin; Kuban-Jankowska, Alicja
One of the main goals of recent bioinorganic chemistry studies has been to design and synthesize novel substances to treat human diseases. The promising compounds are metal-based and metal ion binding components such as vanadium-based compounds. The potential anticancer action of vanadium-based compounds is one of area of investigation in this field. In this study, we present five oxovanadium(IV) and dioxovanadium(V) complexes as potential PTP1B inhibitors with anticancer activity against the MCF-7 breast cancer cell line, the triple negative MDA-MB-231 breast cancer cell line, and the human keratinocyte HaCaT cell line. We observed that all tested compounds were effective inhibitors of PTP1B, which correlates with anticancer activity. [VO(dipic)(dmbipy)]·2 H2O (Compound 4) and [VOO(dipic)](2-phepyH)·H2O (Compound 5) possessed the greatest inhibitory effect, with IC50 185.4 ± 9.8 and 167.2 ± 8.0 nM, respectively. To obtain a better understanding of the relationship between the structure of the examined compounds and their activity, we performed a computer simulation of their binding inside the active site of PTP1B. We observed a stronger binding of complexes containing dipicolinic acid with PTP1B. Based on our simulations, we suggested that the studied complexes exert their activity by stabilizing the WPD-loop in an open position and limiting access to the P-loop.