A novel carbohydrate derived compound FCP5 causes DNA strand breaks and oxidative modifications of DNA bases in cancer cells

Czubatka, Anna; Sarnik, Joanna; Lucent, Del; Błasiak, Janusz; Witczak, Zbigniew J.; Popławski, Tomasz

doi:10.1016/j.cbi.2014.12.023

Cited by 11 publications

(4 citation statements)

References 47 publications

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“…There have been some reports [ 18 , 19 ] showing the ability of thio-sugars to impede cancer cell growth. It was shown that functionalized thio-sugars have cytotoxic properties and therapeutic potential as anticancer agents [ 20 ]. Thio-sugars and iminosugars are potentially useful in the treatment of diabetes and some bacterial and viral infection diseases [ 5 , 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

et al. 2017

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Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 ≤ 50 µM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

et al. 2017

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“…Next, the cells were lysed for 1 h, at 4°C in a lysis buffer (2.5 M NaCl, 100 mM EDTA, 1% Triton X-100, 10 mM Tris, pH 10). All remaining steps including electrophoresis, DAPI comet staining, and measuring were performed according to Czubatka et al 20 …”

Section: Methodsmentioning

confidence: 99%

Packed Red Blood Cell Supernatants Do Not Promote Growth or Cisplatin Resistance of Myeloid Leukemia K-562 Cells

Czubak-Prowizor¹,

Macieja²,

Popławski³

et al. 2022

JBM

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Background A decreased immune surveillance as a consequence of packed red blood cell (PRBC) transfusions has been linked to cancer recurrence and progression, but a causal mechanism remains unclear. During processing and storage of PRBC, numerous bioactive substances accumulate in the acellular fraction (supernatant) of PRBC. Aim The study aimed to determine whether the supernatant of leukocyte-reduced (LR) and non-leukocyte-reduced (NLR) long-stored PRBC can modulate the survival and proliferation of myeloid leukemia K-562 cells, and the influence of cisplatin (cisPt) on these processes. Methods Viability, proliferation, DNA damage, intracellular reactive oxygen species (ROS), caspase-3/7 and caspase-9 levels were determined in response to the LR or NLR, fresh (day 1) and long-stored (day 42) PRBCs. Results The supernatants of fresh (day 1) and stored (day 42) PRBC, in the absence and presence of cisPt, promoted apoptosis of K-562 cells via the increased production of reactive oxygen species (ROS) and increased level of DNA damage, which was manifested by the viability reduction and inhibition of K-562 cell proliferation. No significant influence of the pre-storage leukocyte-filtration and storage time of PRBC units on their anti-proliferative effect was demonstrated. Conclusion The findings may suggest that the PRBC acellular fraction does not affect chronic myeloid leukemia (CML) progression. However, these issues are pioneering and require further study.

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“…Next, the cells were lysed for 1 h, at 4˚C in a lysis buffer (2.5 M NaCl, 100 mM EDTA, 1% Triton X-100, 10 mM Tris, pH 10). All remaining steps including electrophoresis, DAPI comet staining, and measuring were performed according to Czubatka et al [21].…”

Section: Comet Assaymentioning

confidence: 99%

Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin

et al. 2022

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Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains unclear. During the preparation and storage of packed red blood cells (PRBCs) bio-active substances accumulate in the acellular fraction (supernatant). Viability, proliferation, reactive oxygen species (ROS) levels, and DNA damage of colon (LoVo) and breast (MCF7) adenocarcinoma cells and non-tumorigenic MCF-10A cell line were determined in response to the supernatants of fresh and long-stored (day 42) PRBCs, leukoreduced (LR) or non-leukoreduced (NLR). The effect of supernatants on the cytotoxicity of cisplatin (cisPt) towards the cells was also examined. Supernatants, especially from a day 1 PRBCs, both LR and NLR, reduced the viability and inhibited proliferation of tumor cells (LoVo, MCF7), accompanying by the excessive ROS production, but these were not the case in MCF-10A. Moreover, supernatants had no effect on the cytotoxicity of cisPt against LoVo and MCF7 cells, while caused increased drug resistance in MCF-10A cells. The findings suggest the acellular fraction of PRBCs does not exhibit any pro-proliferative activity in the cancer cell lines studied. However, these are pioneering issues and require further research.

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A novel carbohydrate derived compound FCP5 causes DNA strand breaks and oxidative modifications of DNA bases in cancer cells

Cited by 11 publications

References 47 publications

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

Packed Red Blood Cell Supernatants Do Not Promote Growth or Cisplatin Resistance of Myeloid Leukemia K-562 Cells

Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin

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