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001-es BibID:	BIBFORM099877
035-os BibID:	(cikkazonosító)813 (scopus)85122509977 (wos)000757043200001
Első szerző:	Kacsir István (vegyész)
Cím:	Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models / Kacsir István, Sipos Adrienn, Bényei Attila, Janka Eszter, Buglyó Péter, Somsák László, Bai Péter, Bokor Éva
Dátum:	2022
ISSN:	1661-6596 1422-0067
Megjegyzések:	Abstract: Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), irid?ium(III) and rhodium(III) half?sandwich?type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long?term cytostatic activity. These structure?activity relationship studies revealed that: 1) osmium(II) p?cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; 2) the biological effect was influenced by the nature of the central azole ring of the ligands?1,2,3?triazole was the most effective, followed by 1,3,4?oxadiazole, while the iso?meric 1,2,4?oxadiazole abolished the cytostatic activity; 3) we found a correlation between the hy?drophobic character of the complexes and their cytostatic activity: compounds with O?benzoyl pro?tective groups on the carbohydrate moiety were active, compared to O?deprotected ones. The best compound, an osmium(II) complex, had an IC50 value of 0.70 ?M. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non?cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid?soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pan?creatic adenocarcinoma, osteosarcoma and Hodgkin's lymphoma cells, but were inactive on pri?mary, non?transformed human fibroblasts, indicating their applicability as potential anticancer agents.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk osmium complex iridium complex ruthenium complex rhodium complex half-sandwich cooperative binding reactive oxygen species production glycosyl heterocycle oxadiazole triazole ovarian cancer Hodgkin's lymphoma osteosarcoma
Megjelenés:	International Journal of Molecular Sciences. - 23 : 2 (2022), p. 1-39. -
További szerzők:	Sipos Adrienn (1984-) (biológus, biotechnológus) Bényei Attila (1962-) (vegyész) Janka Eszter Anna (1989-) (bőrgyógyász, népegészségügyi szakember) Buglyó Péter (1965-) (vegyész) Somsák László (1954-) (vegyész) Bai Péter (1976-) (biokémikus) Bokor Éva (1982-) (vegyész)
Pályázati támogatás:	K123975 OTKA FK125067 OTKA TKP2020-IKA-04 MTA
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001-es BibID:	BIBFORM117681
035-os BibID:	(WoS)001138525600001 (Scopus)85181969555
Első szerző:	Szeőcs Dóra (PhD hallgató)
Cím:	Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFbeta-ERK signalling / Szeőcs D., Vida B., Petővári G., Póliska Sz., Janka E., Sipos A., Uray K., Sebestyén A., Krasznai Z., Bai P.
Dátum:	2024
ISSN:	2509-2715 2509-2723
Megjegyzések:	Ascites plays a key role in supporting the metastatic potential of ovarian cancer cells. Shear stress and carry-over of cancer cells by ascites flow support carcinogenesis and metastasis formation. In addition, soluble factors may participate in the procarcinogenic effects of ascites in ovarian cancer. This study aimed to determine the biological effects of cell-free ascites on carcinogenesis in ovarian cancer cells. Cell-free ascites from ovarian cancer patients (ASC) non-selectively induced cell proliferation in multiple models of ovarian cancer and untransformed primary human dermal fibroblasts. Furthermore, ASC induced a Warburg-type rearrangement of cellular metabolism in A2780 ovarian cancer cells characterized by increases in cellular oxygen consumption and glycolytic flux; increases in glycolytic flux were dominant. ASC induced mitochondrial uncoupling and fundamentally reduced fatty acid oxidation. Ascites-elicited effects were uniform among ascites specimens. ASC-elicited transcriptomic changes in A2780 ovarian cancer cells included induction of the TGF beta-ERK/MEK pathway, which plays a key role in inducing cell proliferation and oncometabolism. ASC-induced gene expression changes, as well as the overexpression of members of the TGF beta signaling system, were associated with poor survival in ovarian cancer patients. We provided evidence that the activation of the autocrine/paracrine of TGF beta signaling system may be present in bladder urothelial carcinoma and stomach adenocarcinoma. Database analysis suggests that the TGF beta system may feed forward bladder urothelial carcinoma and stomach adenocarcinoma. Soluble components of ASC support the progression of ovarian cancer. These results suggest that reducing ascites production may play an essential role in the treatment of ovarian cancer by inhibiting the progression and reducing the severity of the disease.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	GeroScience. - [Epub ahead of print] (2024). -
További szerzők:	Vida Beáta (1994-) (szülészet-nőgyógyászat) Petővári Gábor Póliska Szilárd (1978-) (biológus) Janka Eszter Anna (1989-) (bőrgyógyász, népegészségügyi szakember) Sipos Adrienn (1984-) (biológus, biotechnológus) Uray Karen (1964-) (biokémikus) Sebestyén Anna Krasznai Zoárd Tibor (1973-) (szülész-nőgyógyász, gyermeknőgyógyász) Bai Péter (1976-) (biokémikus)
Pályázati támogatás:	K142141 NKFIH FK128387 NKFIH FK146852 NKFIH TKP2021-EGA-19 NKFIH TKP2021-EGA-20 NKFIH POST-COVID2021-33 Egyéb NKM2022-30 Egyéb
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001-es BibID:	BIBFORM113864
035-os BibID:	(cikkazonosító)5898 (WoS)001045616200001 (Scopus)85167818337
Első szerző:	Ujlaki Gyula (molekuláris biológus)
Cím:	Identification of bacterial metabolites modulating breast cancer cell proliferation and epithelial-mesenchymal transition / Ujlaki Gy., Kovács T., Vida A., Kókai E., Rauch B., Schwarcz Sz., Mikó E., Janka E., Sipos A., Hegedűs Cs., Uray K., Nagy P., Bai P.
Dátum:	2023
ISSN:	1420-3049
Megjegyzések:	Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol-d-mannose, 1-butanol-butyric acid, ethylene glycol-glycolic acid-oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Molecules. - 28 : 15 (2023), p. 1-18. -
További szerzők:	Kovács Tünde (1990-) (biokémikus, molekuláris biológus) Vida András (1979-) (molekuláris biológus, genetikus) Kókai Endre (1971-) (biokémikus, biológus) Rauch Boglárka (1995-) (molekuláris biológus) Schwarcz Szandra (1988-) (PhD hallgató) Mikó Edit (1980-) (biológus) Janka Eszter Anna (1989-) (bőrgyógyász, népegészségügyi szakember) Sipos Adrienn (1984-) (biológus, biotechnológus) Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Uray Karen (1964-) (biokémikus) Nagy Péter (1971-) (biofizikus) Bai Péter (1976-) (biokémikus)
Pályázati támogatás:	K123975 NKFIH K142141 NKFIH FK128387 NKFIH POST-COVID2021-33 Egyéb TKP2021-EGA-19 Egyéb TKP2021-EGA-20 Egyéb TKP2021-EGA Egyéb
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