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Papers by Jagoda Adamczyk-Grochala

Research paper thumbnail of TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Research paper thumbnail of Knockout of TRDMT1 methyltransferase affects DNA methylome in glioblastoma cells

Journal of Neuro-Oncology

Purpose We have previously shown that TRDMT1 methyltransferase is a regulator of chemotherapy-ass... more Purpose We have previously shown that TRDMT1 methyltransferase is a regulator of chemotherapy-associated responses in glioblastoma cells. Despite the fact that glioblastoma, a common and malignant brain tumor, is widely characterized in terms of genetic and epigenetic markers, there are no data on TRDMT1-related changes in 5-methylcytosine pools in the genome. In the present study, the effect of TRDMT1 gene knockout (KO) on DNA methylome was analyzed. Methods CRISPR-based approach was used to obtain TRDMT1 KO glioblastoma cells. Total 5-methylcytosine levels in DNA, DNMT1 pools and DNMT activity were studied using ELISA. Reduced representation bisulfite sequencing (RRBS) was considered to comprehensively evaluate DNA methylome in glioblastoma cells with TRDMT1 KO. Results TRDMT1 KO cells were characterized by decreased levels of total 5-methylcytosine in DNA and DNMT1, and DNMT activity. RRBS-based methylome analysis revealed statistically significant differences in methylation-rele...

Research paper thumbnail of Synergic Temperature Effect of Star-like Monodisperse Iron Oxide Nanoparticles and Their Related Responses in Normal and Cancer Cells

The Journal of Physical Chemistry B

Research paper thumbnail of Lapatinib- and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status

Research paper thumbnail of DNMT2/TRDMT1 gene knockout compromises doxorubicin-induced unfolded protein response and sensitizes cancer cells to ER stress-induced apoptosis

Apoptosis

The acidic, hypoxic and nutrient-deprived tumor microenvironment may induce endoplasmic reticulum... more The acidic, hypoxic and nutrient-deprived tumor microenvironment may induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may exert an important cytoprotective role by promoting folding of newly synthesized proteins and cancer cell survival. The lack of DNMT2/TRDMT1 methyltransferase-mediated C38 tRNA methylation compromises translational fidelity that may result in the accumulation of misfolded and aggregated proteins leading to proteotoxic stress-related cell death. In the present study, DNMT2/TRDMT1 gene knockout-mediated effects were investigated during doxorubicin (DOX)-induced ER stress and PERK-, IRE1- and ATF6-orchestrated UPR in four genetically different cellular models of cancer (breast and cervical cancer, osteosarcoma and glioblastoma cells). Upon DOX stimulation, DNMT2/TRDMT1 gene knockout impaired PERK activation and modulated NSUN and 5-methylcytosine RNA-based responses and microRNA profiles. The lack of DNMT2/TRDMT1 gene in DOX-treated f...

Research paper thumbnail of 5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

Research paper thumbnail of Deficiency of TRDMT1 impairs exogenous RNA-based response and promotes retrotransposon activity during long-term culture of osteosarcoma cells

Research paper thumbnail of Senolysis-Based Elimination of Chemotherapy-Induced Senescent Breast Cancer Cells by Quercetin Derivative with Blocked Hydroxy Groups

Cancers

Drug-induced senescence program may be activated both in normal and cancer cells as a consequence... more Drug-induced senescence program may be activated both in normal and cancer cells as a consequence of chemotherapeutic treatment, leading to some adverse side effects such as senescence-associated secretory phenotype (SASP), secondary senescence, and cancer promotion. Targeted elimination of senescent cells can be achieved by drugs with senolytic activity (senolytics), for example, the plant-derived natural compound quercetin, especially when co-treated with kinase inhibitor dasatinib. In the present study, three quercetin derivatives were synthesized and tested for improved senolytic action against etoposide-induced senescent human normal mammary epithelial cells and triple-negative breast cancer cells in vitro. Transformation of catechol moiety into diphenylmethylene ketal and addition of three acetyl groups to the quercetin molecule (QD3 derivative) promoted the clearance of senescent cancer cells as judged by increased apoptosis compared to etoposide-treated cells. A QD3-mediated...

Research paper thumbnail of The lack of functional DNMT2/TRDMT1 gene modulates cancer cell responses during drug-induced senescence

Aging

Cellular senescence may be a side effect of chemotherapy and other anti-cancer treatments that ma... more Cellular senescence may be a side effect of chemotherapy and other anti-cancer treatments that may promote inflammation and paracrine secondary senescence in healthy tissues. DNMT2/TRDMT1 methyltransferase is implicated in the regulation of cellular lifespan and DNA damage response (DDR). In the present study, the responses to senescence inducing concentrations of doxorubicin and etoposide in different cancer cells with DNMT2/TRDMT1 gene knockout were evaluated, namely changes in the cell cycle, apoptosis, autophagy, interleukin levels, genetic stability and DDR, and 5-mC and NSUN1-6 levels. Moreover, the effect of azacytidine post-treatment was considered. Diverse responses were revealed that was based on type of cancer cells (breast and cervical cancer, osteosarcoma and glioblastoma cells) and anti-cancer drugs. DNMT2/TRDMT1 gene knockout in drug-treated glioblastoma cells resulted in decreased number of apoptotic and senescent cells, IL-8 levels and autophagy, and increased number of necrotic cells, DNA damage and affected DDR compared to drug-treated glioblastoma cells with unmodified levels of DNMT2/TRDMT1. We suggest that DNMT2/TRDMT1 gene knockout in selected experimental settings may potentiate some adverse effects associated with chemotherapy-induced senescence.

Research paper thumbnail of Multimodal polymer encapsulated CdSe/Fe3O4 nanoplatform with improved biocompatibility for two-photon and temperature stimulated bioapplications

Materials Science and Engineering: C

Research paper thumbnail of Silver birch pollen-derived microRNAs promote NF-κB-mediated inflammation in human lung cells

Science of The Total Environment

Research paper thumbnail of Remifentanil preconditioning protects against hypoxia-induced senescence and necroptosis in human cardiac myocytes in vitro

Research paper thumbnail of Nano-Based Theranostic Tools for the Detection and Elimination of Senescent Cells

Cells

The progressive accumulation of apoptosis-resistant and secretory active senescent cells (SCs) in... more The progressive accumulation of apoptosis-resistant and secretory active senescent cells (SCs) in animal and human aged tissues may limit lifespan and healthspan and lead to age-related diseases such as cancer, neurodegenerative disorders, and metabolic syndrome. Thus, SCs are suggested targets in anti-aging therapy. In the last two decades, a number of nanomaterials have gained much attention as innovative tools in theranostic applications due to their unique properties improving target visualization, drug and gene delivery, controlled drug release, effective diagnosis, and successful therapy. Although the healthcare industry has focused on a plethora of applications of nanomaterials, it remains elusive how nanomaterials may modulate cellular senescence, a hallmark of aging. In this review paper, we consider novel nanotechnology-based strategies for healthspan promotion and the prevention of age-related dysfunctions that are based on the delivery of therapeutic compounds capable to...

Research paper thumbnail of Correction to “Energy Conversion and Biocompatibility of Surface Functionalized Magnetite Nanoparticles with Phosphonic Moieties”

The Journal of Physical Chemistry B

Metrics & More Article Recommendations One of the author names was misspelled in the final public... more Metrics & More Article Recommendations One of the author names was misspelled in the final publication. Grzegorz Litwienienko should be Grzegorz Litwinienko. This is corrected in the authorship of this Correction.

Research paper thumbnail of Energy Conversion and Biocompatibility of Surface Functionalized Magnetite Nanoparticles with Phosphonic Moieties

Research paper thumbnail of Treatment with Modified Extracts of the Microalga Planktochlorella nurekis Attenuates the Development of Stress-Induced Senescence in Human Skin Cells

Nutrients

More recently, we have proposed a safe non-vector approach to modifying the biochemical profiles ... more More recently, we have proposed a safe non-vector approach to modifying the biochemical profiles of the microalga Planktochlorella nurekis and obtained twelve clones with improved content of lipids and selected pigments and B vitamins and antioxidant activity compared to unaffected cells. In the present study, the biological activity of water and ethanolic extracts of modified clones is investigated in the context of their applications in the cosmetic industry and regenerative medicine. Extract-mediated effects on cell cycle progression, proliferation, migration, mitogenic response, apoptosis induction, and oxidative and nitrosative stress promotion were analyzed in normal human fibroblasts and keratinocytes in vitro. Microalgal extracts did not promote cell proliferation and were relatively non-cytotoxic when short-term treatment was considered. Long-term stimulation with selected microalgal extracts attenuated the development of oxidative stress-induced senescence in skin cells th...

Research paper thumbnail of AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts

Research paper thumbnail of c-Myc activation promotes cofilin-mediated F-actin cytoskeleton remodeling and telomere homeostasis as a response to oxidant-based DNA damage in medulloblastoma cells

Research paper thumbnail of Snake venoms promote stress-induced senescence in human fibroblasts

Journal of Cellular Physiology

Research paper thumbnail of Phytochemical-induced nucleolar stress results in the inhibition of breast cancer cell proliferation

Redox Biology

The nucleolus is a stress sensor and compromised nucleolar activity may be considered as an attra... more The nucleolus is a stress sensor and compromised nucleolar activity may be considered as an attractive anticancer strategy. In the present study, the effects of three plant-derived natural compounds, i.e., sulforaphane (SFN), ursolic acid (UA) and betulinic acid (BA) on nucleolar state were investigated in breast cancer cell lines of different receptor status, namely MCF-7, MDA-MB-231 and SK-BR-3 cells. Cytostatic action of phytochemicals against breast cancer cells was observed at low micromolar concentration window (5-20 µM) and mediated by elevated p21 levels, and cell proliferation of SFN-, UA-and BA-treated normal human mammary epithelial cells (HMEC) was unaffected. Phytochemical-mediated inhibition of cell proliferation was accompanied by increased levels of superoxide and protein carbonylation that lead to disorganization of A-and B-type lamin networks and alterations in the nuclear architecture. Phytochemicals promoted nucleolar stress as judged by the nucleoplasmic translocation of RNA polymerase I-specific transcription initiation factor RRN3/ TIF-IA, inhibition of new rRNA synthesis and decrease in number of nucleoli. Phytochemicals also decreased the levels of NOP2, proliferation-associated nucleolar protein p120, and WDR12 required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome, and phosphorylation of S6 ribosomal protein that may result in diminished translation and inhibition of cell proliferation. In summary, three novel ribotoxic stress stimuli were revealed with a potential to be used in nucleolus-focused anticancer therapy.

Research paper thumbnail of TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

Research paper thumbnail of Knockout of TRDMT1 methyltransferase affects DNA methylome in glioblastoma cells

Journal of Neuro-Oncology

Purpose We have previously shown that TRDMT1 methyltransferase is a regulator of chemotherapy-ass... more Purpose We have previously shown that TRDMT1 methyltransferase is a regulator of chemotherapy-associated responses in glioblastoma cells. Despite the fact that glioblastoma, a common and malignant brain tumor, is widely characterized in terms of genetic and epigenetic markers, there are no data on TRDMT1-related changes in 5-methylcytosine pools in the genome. In the present study, the effect of TRDMT1 gene knockout (KO) on DNA methylome was analyzed. Methods CRISPR-based approach was used to obtain TRDMT1 KO glioblastoma cells. Total 5-methylcytosine levels in DNA, DNMT1 pools and DNMT activity were studied using ELISA. Reduced representation bisulfite sequencing (RRBS) was considered to comprehensively evaluate DNA methylome in glioblastoma cells with TRDMT1 KO. Results TRDMT1 KO cells were characterized by decreased levels of total 5-methylcytosine in DNA and DNMT1, and DNMT activity. RRBS-based methylome analysis revealed statistically significant differences in methylation-rele...

Research paper thumbnail of Synergic Temperature Effect of Star-like Monodisperse Iron Oxide Nanoparticles and Their Related Responses in Normal and Cancer Cells

The Journal of Physical Chemistry B

Research paper thumbnail of Lapatinib- and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status

Research paper thumbnail of DNMT2/TRDMT1 gene knockout compromises doxorubicin-induced unfolded protein response and sensitizes cancer cells to ER stress-induced apoptosis

Apoptosis

The acidic, hypoxic and nutrient-deprived tumor microenvironment may induce endoplasmic reticulum... more The acidic, hypoxic and nutrient-deprived tumor microenvironment may induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may exert an important cytoprotective role by promoting folding of newly synthesized proteins and cancer cell survival. The lack of DNMT2/TRDMT1 methyltransferase-mediated C38 tRNA methylation compromises translational fidelity that may result in the accumulation of misfolded and aggregated proteins leading to proteotoxic stress-related cell death. In the present study, DNMT2/TRDMT1 gene knockout-mediated effects were investigated during doxorubicin (DOX)-induced ER stress and PERK-, IRE1- and ATF6-orchestrated UPR in four genetically different cellular models of cancer (breast and cervical cancer, osteosarcoma and glioblastoma cells). Upon DOX stimulation, DNMT2/TRDMT1 gene knockout impaired PERK activation and modulated NSUN and 5-methylcytosine RNA-based responses and microRNA profiles. The lack of DNMT2/TRDMT1 gene in DOX-treated f...

Research paper thumbnail of 5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

Research paper thumbnail of Deficiency of TRDMT1 impairs exogenous RNA-based response and promotes retrotransposon activity during long-term culture of osteosarcoma cells

Research paper thumbnail of Senolysis-Based Elimination of Chemotherapy-Induced Senescent Breast Cancer Cells by Quercetin Derivative with Blocked Hydroxy Groups

Cancers

Drug-induced senescence program may be activated both in normal and cancer cells as a consequence... more Drug-induced senescence program may be activated both in normal and cancer cells as a consequence of chemotherapeutic treatment, leading to some adverse side effects such as senescence-associated secretory phenotype (SASP), secondary senescence, and cancer promotion. Targeted elimination of senescent cells can be achieved by drugs with senolytic activity (senolytics), for example, the plant-derived natural compound quercetin, especially when co-treated with kinase inhibitor dasatinib. In the present study, three quercetin derivatives were synthesized and tested for improved senolytic action against etoposide-induced senescent human normal mammary epithelial cells and triple-negative breast cancer cells in vitro. Transformation of catechol moiety into diphenylmethylene ketal and addition of three acetyl groups to the quercetin molecule (QD3 derivative) promoted the clearance of senescent cancer cells as judged by increased apoptosis compared to etoposide-treated cells. A QD3-mediated...

Research paper thumbnail of The lack of functional DNMT2/TRDMT1 gene modulates cancer cell responses during drug-induced senescence

Aging

Cellular senescence may be a side effect of chemotherapy and other anti-cancer treatments that ma... more Cellular senescence may be a side effect of chemotherapy and other anti-cancer treatments that may promote inflammation and paracrine secondary senescence in healthy tissues. DNMT2/TRDMT1 methyltransferase is implicated in the regulation of cellular lifespan and DNA damage response (DDR). In the present study, the responses to senescence inducing concentrations of doxorubicin and etoposide in different cancer cells with DNMT2/TRDMT1 gene knockout were evaluated, namely changes in the cell cycle, apoptosis, autophagy, interleukin levels, genetic stability and DDR, and 5-mC and NSUN1-6 levels. Moreover, the effect of azacytidine post-treatment was considered. Diverse responses were revealed that was based on type of cancer cells (breast and cervical cancer, osteosarcoma and glioblastoma cells) and anti-cancer drugs. DNMT2/TRDMT1 gene knockout in drug-treated glioblastoma cells resulted in decreased number of apoptotic and senescent cells, IL-8 levels and autophagy, and increased number of necrotic cells, DNA damage and affected DDR compared to drug-treated glioblastoma cells with unmodified levels of DNMT2/TRDMT1. We suggest that DNMT2/TRDMT1 gene knockout in selected experimental settings may potentiate some adverse effects associated with chemotherapy-induced senescence.

Research paper thumbnail of Multimodal polymer encapsulated CdSe/Fe3O4 nanoplatform with improved biocompatibility for two-photon and temperature stimulated bioapplications

Materials Science and Engineering: C

Research paper thumbnail of Silver birch pollen-derived microRNAs promote NF-κB-mediated inflammation in human lung cells

Science of The Total Environment

Research paper thumbnail of Remifentanil preconditioning protects against hypoxia-induced senescence and necroptosis in human cardiac myocytes in vitro

Research paper thumbnail of Nano-Based Theranostic Tools for the Detection and Elimination of Senescent Cells

Cells

The progressive accumulation of apoptosis-resistant and secretory active senescent cells (SCs) in... more The progressive accumulation of apoptosis-resistant and secretory active senescent cells (SCs) in animal and human aged tissues may limit lifespan and healthspan and lead to age-related diseases such as cancer, neurodegenerative disorders, and metabolic syndrome. Thus, SCs are suggested targets in anti-aging therapy. In the last two decades, a number of nanomaterials have gained much attention as innovative tools in theranostic applications due to their unique properties improving target visualization, drug and gene delivery, controlled drug release, effective diagnosis, and successful therapy. Although the healthcare industry has focused on a plethora of applications of nanomaterials, it remains elusive how nanomaterials may modulate cellular senescence, a hallmark of aging. In this review paper, we consider novel nanotechnology-based strategies for healthspan promotion and the prevention of age-related dysfunctions that are based on the delivery of therapeutic compounds capable to...

Research paper thumbnail of Correction to “Energy Conversion and Biocompatibility of Surface Functionalized Magnetite Nanoparticles with Phosphonic Moieties”

The Journal of Physical Chemistry B

Metrics & More Article Recommendations One of the author names was misspelled in the final public... more Metrics & More Article Recommendations One of the author names was misspelled in the final publication. Grzegorz Litwienienko should be Grzegorz Litwinienko. This is corrected in the authorship of this Correction.

Research paper thumbnail of Energy Conversion and Biocompatibility of Surface Functionalized Magnetite Nanoparticles with Phosphonic Moieties

Research paper thumbnail of Treatment with Modified Extracts of the Microalga Planktochlorella nurekis Attenuates the Development of Stress-Induced Senescence in Human Skin Cells

Nutrients

More recently, we have proposed a safe non-vector approach to modifying the biochemical profiles ... more More recently, we have proposed a safe non-vector approach to modifying the biochemical profiles of the microalga Planktochlorella nurekis and obtained twelve clones with improved content of lipids and selected pigments and B vitamins and antioxidant activity compared to unaffected cells. In the present study, the biological activity of water and ethanolic extracts of modified clones is investigated in the context of their applications in the cosmetic industry and regenerative medicine. Extract-mediated effects on cell cycle progression, proliferation, migration, mitogenic response, apoptosis induction, and oxidative and nitrosative stress promotion were analyzed in normal human fibroblasts and keratinocytes in vitro. Microalgal extracts did not promote cell proliferation and were relatively non-cytotoxic when short-term treatment was considered. Long-term stimulation with selected microalgal extracts attenuated the development of oxidative stress-induced senescence in skin cells th...

Research paper thumbnail of AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts

Research paper thumbnail of c-Myc activation promotes cofilin-mediated F-actin cytoskeleton remodeling and telomere homeostasis as a response to oxidant-based DNA damage in medulloblastoma cells

Research paper thumbnail of Snake venoms promote stress-induced senescence in human fibroblasts

Journal of Cellular Physiology

Research paper thumbnail of Phytochemical-induced nucleolar stress results in the inhibition of breast cancer cell proliferation

Redox Biology

The nucleolus is a stress sensor and compromised nucleolar activity may be considered as an attra... more The nucleolus is a stress sensor and compromised nucleolar activity may be considered as an attractive anticancer strategy. In the present study, the effects of three plant-derived natural compounds, i.e., sulforaphane (SFN), ursolic acid (UA) and betulinic acid (BA) on nucleolar state were investigated in breast cancer cell lines of different receptor status, namely MCF-7, MDA-MB-231 and SK-BR-3 cells. Cytostatic action of phytochemicals against breast cancer cells was observed at low micromolar concentration window (5-20 µM) and mediated by elevated p21 levels, and cell proliferation of SFN-, UA-and BA-treated normal human mammary epithelial cells (HMEC) was unaffected. Phytochemical-mediated inhibition of cell proliferation was accompanied by increased levels of superoxide and protein carbonylation that lead to disorganization of A-and B-type lamin networks and alterations in the nuclear architecture. Phytochemicals promoted nucleolar stress as judged by the nucleoplasmic translocation of RNA polymerase I-specific transcription initiation factor RRN3/ TIF-IA, inhibition of new rRNA synthesis and decrease in number of nucleoli. Phytochemicals also decreased the levels of NOP2, proliferation-associated nucleolar protein p120, and WDR12 required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome, and phosphorylation of S6 ribosomal protein that may result in diminished translation and inhibition of cell proliferation. In summary, three novel ribotoxic stress stimuli were revealed with a potential to be used in nucleolus-focused anticancer therapy.