Anna Paszel-Jaworska

Poznan University of Medical Sciences

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Aleksandra Romaniuk

Poznan University of Medical Sciences

Błażej Rubiś

Poznan University of Medical Sciences

Maria Rybczyńska

Poznan University of Medical Sciences

Mariusz Kaczmarek

Poznan University of Medical Sciences

Ewa Totoń

Poznan University of Medical Sciences

Natalia Lipińska

Poznan University of Medical Sciences

Natalia Lisiak

Poznan University of Medical Sciences

M. Jurczyk

Poznan University of Medical Sciences

Lucjusz Zaprutko

Poznan University of Medical Sciences

Paulina Urbaniak

Poznan University of Medical Sciences

Cooperative Institutions

Poznan University of Medical Sciences

Polish Academy of Sciences

Poznań University of Technology

University of Life Sciences in Poznań

Institute of Natural Fibres and Medicinal Plants

Heliodor Swiecicki Clinical Hospital

Institute of Plant Genetics, Polish Academy of Sciences

Greater Poland Cancer Center

Weatherford College

Centrum Onkologii

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New therapies targeting aging cells in the skin

Journal of Medical Science (2023)

Anna Paszel-Jaworska Justyna Gornowicz‐Porowska Aleksandra Dańczak‐Pazdrowska Adriana Polańska Violetta Krajka‐Kuźniak

Senescence is accompanied by numerous processes that lead to alterations in cell metabolism, cell cycle arrest, and, increased production and secretion of senescence-associated secretory phenotype (SASP). Consequently, signaling pathways cascades are activated, leading to inflammation that can trigger multiple disorders, including cancer. Recently, a novel therapeutic approach was proposed based on targeting senescent cells using senolytics. This group of biologically active compounds includes fisetin, quercetin, dasatinib, and others. These compounds were shown to affect laboratory animals (rodents) by improving the quality of life and significantly increasing the length of life by reducing senescent cells pool in different organs. Based on these findings, we decided to evaluate the potential of these compounds in targeting senescent cells in human skin using in vitro model based on human-derived keratinocytes (HEKa) and fibroblasts (HDFa). Cytotoxicity assay revealed that the activity of the compounds was time- and dose-dependent as well as cell-type dependent. Further studies were performed to reveal the mechanistic aspect of these observations including assessment of the senescence marker, namely p16. However, it requires clarification before entering clinical trials to provide not only efficient but, first of all, safe application of senolytics to human skin.

Fisetin

Senescence

10.20883/medical.e903

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Cytotoxic activity of stigmasteryl esters and products of their thermo-oxidative degradation against drug sensitive and drug resistant human acute lymphoblastic leukemia cells

Acta Scientiarum Polonorum Technologia Alimentaria (2018)

Marianna Raczyk Anna Paszel-Jaworska Magdalena Rudzińska

Phytosterols are mainly known as a cholesterol-lowering factor, although they form oxidation products during food storage and processing. Moreover, phytosterol oxidation products (POP) can be ab- sorbed and found in human serum, so there is the need to investigate their impact on different kinds of cells.Esters of fatty acids (oleic, linoleic and linolenic) with stigmasterol were synthetized and heated at 180°C, for 1–12 hours. The cytotoxic effect on the leukemic cells of unheated stigmasteryl esters and the mixture of compounds after heating was determined using MTT assays. POP were identified using GC-MS. The total number of POP was analysed by SPE fractionation and GC-FID separation. Dimers, trimers and oligomers in non-polar fraction were determined by gel permeation chromatography with refractive index detection.After heating, stigmasterol oxidation products were formed (up to 1.1 mg/g ester). The heating increased the potency of the compounds to reduce cell population and form POPs and oligomers in a time-dependent manner.The cytotoxicity depends on the kind of ester, dose and time. The strongest cytotoxic effect was found after 72 hours of cell treatment. Among the three stigmasteryl esters tested the most cytotoxic effect was caused by stigmasteryl linoleate.

Stigmasterol

Gel permeation chromatography

Chlorobenzene

10.17306/j.afs.0516

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Citations (7)

Effect of 3-O-acetylaleuritolic acid from in vitro-cultured Drosera spatulata on cancer cells survival and migration

Pharmacological Reports (2020)

Ewa Totoń Izabela Kędziora Aleksandra Romaniuk Natalia Konieczna Mariusz Kaczmarek

Clonogenic assay

HeLa

MTT assay

Viability assay

10.1007/s43440-019-00008-x

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Citations (4)

Cytotoxic activity of stigmasteryl esters and products of their thermo-oxidative degradation against drug sensitive and drug resistant human acute lymphoblastic leukemia cells [pdf]

Acta Scientiarum Polonorum Technologia Alimentaria (2018)

Marianna Raczyk Anna Paszel-Jaworska Magdalena Rudzińska

Background.Phytosterols are mainly known as a cholesterol-lowering factor, although they form oxidation products during food storage and processing.Moreover, phytosterol oxidation products (POP) can be absorbed and found in human serum, so there is the need to investigate their impact on different kinds of cells.Material and methods.Esters of fatty acids (oleic, linoleic and linolenic) with stigmasterol were synthetized and heated at 180°C, for 1-12 hours.The cytotoxic effect on the leukemic cells of unheated stigmasteryl esters and the mixture of compounds after heating was determined using MTT assays.POP were identified using GC-MS.The total number of POP was analysed by SPE fractionation and GC-FID separation.Dimers, trimers and oligomers in non-polar fraction were determined by gel permeation chromatography with refractive index detection.Results.After heating, stigmasterol oxidation products were formed (up to 1.1 mg/g ester).The heating increased the potency of the compounds to reduce cell population and form POPs and oligomers in a timedependent manner. Conclusion.The cytotoxicity depends on the kind of ester, dose and time.The strongest cytotoxic effect was found after 72 hours of cell treatment.Among the three stigmasteryl esters tested the most cytotoxic effect was caused by stigmasteryl linoleate.

Degradation

10.17306/j.afs.2018.0516

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Citations (2)

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

Chemico-Biological Interactions (2015)

Anna Paszel-Jaworska Błażej Rubiś Barbara Bednarczyk–Cwynar Lucjusz Zaprutko Maria Rybczyńska

ABCC1

10.1016/j.cbi.2015.07.011

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Citations (17)

Telomerase Inhibitor TMPyP4 Alters Adhesion and Migration of Breast-Cancer Cells MCF7 and MDA-MB-231

International Journal of Molecular Sciences (2019)

Natalia Konieczna Aleksandra Romaniuk Natalia Lisiak Ewa Totoń Anna Paszel-Jaworska

Human telomeres were one of the first discovered and characterized sequences forming quadruplex structures. Association of these structures with oncogenic and tumor suppressor proteins suggests their important role in cancer development and therapy efficacy. Since cationic porphyrin TMPyP4 is known as G-quadruplex stabilizer and telomerase inhibitor, the aim of the study was to analyze the anticancer properties of this compound in two different human breast-cancer MCF7 and MDA-MB-231 cell lines. The cytotoxicity of TMPyP4 alone or in combination with doxorubicin was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) and clonogenic assays, and the cell-cycle alterations were analyzed by flow cytometry. Telomerase expression and activity were evaluated using qPCR and telomeric repeat amplification protocol (TRAP) assays, respectively. The contribution of G-quadruplex inhibitor to protein pathways engaged in cell survival, DNA repair, adhesion, and migration was performed using immunodetection. Scratch assay and functional assessment of migration and cell adhesion were also performed. Consequently, it was revealed that in the short term, TMPyP4 neither revealed cytotoxic effect nor sensitized MCF7 and MDA-MB-231 to doxorubicin, but altered breast-cancer cell adhesion and migration. It suggests that TMPyP4 might substantially contribute to a significant decrease in cancer cell dissemination and, consequently, cancer cell survival reduction. Importantly, this effect might not be associated with telomeres or telomerase.

Clonogenic assay

MTT assay

10.3390/ijms20112670

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Citations (35)

LEP (−2548G>A LEP) and LEPR (223Gln>Arg, 109Lys>Arg) polymorphisms as breast cancer risk factors in the Polish female population

Molecular Biology Reports (2021)

Hanna Hołysz Anna Paszel-Jaworska Aleksandra Romaniuk Sylwia Grodecka-Gazdecka Błażej Rubiś

On a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. The study involved 209 women aged 59.6 ± 11 years diagnosed with breast cancer and 202 healthy women aged 57.8 ± 8.2 years, who were blood donors. Polymorphism were evaluated by PCR-RFLP reaction followed by the verification of part of the samples by sequencing. The results of the study confirmed obesity as a significant breast cancer development risk factor in Polish women. However, no significant association between the studied polymorphisms and breast cancer risk or severity of the neoplastic disease was found. Interestingly, it was shown that wild type 223Gln>Gln leptin receptor (LEPR) was statistically more common in women with human epidermal growth factor receptor 2 negative (HER2-) than human epidermal groth factor receptor 2 positive (HER2+) breast cancer and wild type form of 2548G>A LEP was more common in women with progesterone receptor positive (PR+) than progesterone receptor negative (PR-) breast cancer. Studied polymorphisms of the LEP and LEPR genes do not increase breast cancer risk in the population of Polish women. However, they can affect PR an HER receptors expression and thus the severity of the disease. Noteworthy, this interesting correlation is being reported for the first time and might constitute an essential contribution to the identification of molecular mechanisms of carcinogenesis.

10.1007/s11033-021-06328-7

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Increased proapoptotic activity of electron beam irradiated doxorubicin and epirubicin in multidrug-resistant human leukemic cells

Chemico-Biological Interactions (2016)

Anna Paszel-Jaworska Ewa Totoń Katarzyna Dettlaff Aleksandra Kaczmarek Waldemar Bednarski

Epirubicin

Viability assay

Radiosensitivity

10.1016/j.cbi.2016.08.011

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Citations (3)