Browsing by Author "Kostrzewa, Tomasz"

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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
Endogenous estrogen metabolites as oxidative stress mediators and endometrial cancer biomarkers
(2024) Bukato, Katarzyna; Kostrzewa, Tomasz; Gammazza, Antonella Marino; Gorska-Ponikowska, Magdalena; Sawicki, Sambor
Background. Endometrial cancer is the most common gynecologic malignancy found in developed countries. Because therapy can be curative at first, early detection and diagnosis are crucial for successful treatment. Early diagnosis allows patients to avoid radical therapies and offers conservative management options. There are currently no proven biomarkers that predict the risk of disease occurrence, enable early identification or support prognostic evaluation. Consequently, there is increasing interest in discovering sensitive and specific biomarkers for the detection of endometrial cancer using noninvasive approaches. Content. Hormonal imbalance caused by unopposed estrogen affects the expression of genes involved in cell proliferation and apoptosis, which can lead to uncontrolled cell growth and carcinogenesis. In addition, due to their ability to cause oxidative stress, estradiol metabolites have both carcinogenic and anticarcinogenic properties. Catechol estrogens are converted to reactive quinones, resulting in oxidative DNA damage that can initiate the carcinogenic process. The molecular anticancer mechanisms are still not fully understood, but it has been established that some estradiol metabolites generate reactive oxygen species and reactive nitrogen species, resulting in nitro-oxidative stress that causes cancer cell cycle arrest or cell death. Therefore, identifying biomarkers that reflect this hormonal imbalance and the presence of endometrial cancer in minimally invasive or noninvasive samples such as blood or urine could significantly improve early detection and treatment outcomes. Summary. This review analyzes the role of estrogen metabolites as potential biomarkers for the early detection and monitoring of endometrial cancer.
Open Access
Green tea catechins induce inhibition of PTP1B phosphatase in breast cancer cells with potent anti-cancer properties : in vitro assay, molecular docking, and dynamics studies
(2020) Kuban-Jankowska, Alicja; Kostrzewa, Tomasz; Musial, Claudia; Barone, Giampaolo; Lo-Bosco, Giosuè; Lo-Celso, Fabrizio; Gorska-Ponikowska, Magdalena
Green tea (Camellia sinesis) is widely known for its anticancer and anti-inflammatory properties. Among the biologically active compounds contained in Camellia sinesis, the main antioxidant agents are catechins. Recent scientific research indicates that the number of hydroxyl groups and the presence of characteristic structural groups have a major impact on the antioxidant activity of catechins. The best source of these compounds is unfermented green tea. Depending on the type and origin of green tea leaves, their antioxidant properties may be uneven. Catechins exhibit the strong property of neutralizing reactive oxygen and nitrogen species. The group of green tea catechin derivatives includes: epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate. The last of these presents the most potent anti-inflammatory and anticancer potential. Notably, green tea catechins are widely described to be efficient in the prevention of lung cancer, breast cancer, esophageal cancer, stomach cancer, liver cancer and prostate cancer. The current review aims to summarize the potential anticancer effects and molecular signaling pathways of major green tea catechins. It needs to be clearly emphasized that green tea as well as green tea catechols cannot replace the standard chemotherapy. Nonetheless, their beneficial effects may support the standard anticancer approach.
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.