γ radiation-induced damage of nucleic acid bases, calf thymus DNA and DNA within MCF-7 breast cancer cells by [Cu2(OAc)4(tnz)2]: a potential radiosensitizer

Santra, Ramesh Chandra; Ganguly, Durba; Bhattacharya, Debalina; Karmakar, Parimal; Saha, Abhijit; Das, Saurabh

doi:10.1039/c7nj02061a

Cited by 4 publications

(27 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21 This was an inspiration toward using complexes of Ornidazole to investigate their radio-sensitizing and/or cytotoxic attributes by bringing about a substantial decrease in RNO 2 •– formation and yet not compromising on efficacy. 26 − 28 , 33 Therefore, like in tirapazamine where 80% of drug metabolism is irrelevant in killing hypoxic cells, here also if we could show that complexes of Onz are better radio-sensitizers or hypoxic cytotoxins in spite of decreased RNO 2 •– , 26 − 28 , 33 the amount required for biological activity can be believed to be provided by the complexes. If the amount formed by Onz is much in excess of what is actually necessary, then there is the risk of undesirable neurotoxic side effects.…”

Section: Introductionmentioning

confidence: 73%

“…Since 5,6-dihydroxy-5,6-dihydrocytosine (cytosine glycol) is unstable and known to convert to 5,6-dihydroxy-5,6-dihydrouracil (uracil glycol) by deamination, we used our existing HPLC method files on uracil to identify the degradation products of cytosine. 33 , 38 A peak in the chromatogram appearing at a retention time close to that of 5,6-dihydroxy-5,6-dihydrouracil as saved in our earlier method file could be due to either 5,6-dihydroxy-5,6-dihydrocytosine or 5,6-dihydroxy-5,6-dihydrouracil (i.e., if it had in the time frame between irradiation of cytosine and performance of HPLC, converted either completely or partially from 5,6-dihydroxy-5,6-dihydrocytosine). 33 , 38 It is known that 5,6-dihydroxy-5,6-dihydrocytosine by dehydration converts to 5-hydroxycytosine or by deamination and dehydration to 5-hydroxyuracil.…”

Section: Results and Discussionmentioning

confidence: 99%

“… 33 , 38 A peak in the chromatogram appearing at a retention time close to that of 5,6-dihydroxy-5,6-dihydrouracil as saved in our earlier method file could be due to either 5,6-dihydroxy-5,6-dihydrocytosine or 5,6-dihydroxy-5,6-dihydrouracil (i.e., if it had in the time frame between irradiation of cytosine and performance of HPLC, converted either completely or partially from 5,6-dihydroxy-5,6-dihydrocytosine). 33 , 38 It is known that 5,6-dihydroxy-5,6-dihydrocytosine by dehydration converts to 5-hydroxycytosine or by deamination and dehydration to 5-hydroxyuracil. 38 Therefore, our uracil method file, created for detecting uracil derivatives, helped us realize an initial formation of 5,6-dihydroxy-5,6-dihydrocytosine that subsequently converts into several uracil derivatives, as mentioned above.…”

Section: Results and Discussionmentioning

confidence: 99%

“…Determination of concentration was possible using standard plots prepared earlier for each nucleobase. 33 In this manner, radiation-induced damage of each nucleobase either in the absence or presence of a compound was obtained.…”

Section: Methodsmentioning

confidence: 99%

“…If the amount formed by Onz is much in excess of what is actually necessary, then there is the risk of undesirable neurotoxic side effects. 26 − 28 , 33 Hence, use of complexes could have the advantage that excess RNO 2 •– would not be present in the system, leading to some clinical success with regard to toxic side effects. 26 − 28 Worth mentioning here is that the complexes are either better DNA-binding agents or DNA-damaging agents or both, following interaction of in situ generated RNO 2 •– with nucleobases and calf thymus DNA.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Radio-Sensitizing Effects of Cu^II and Zn^II Complexes of Ornidazole: Role of Nitro Radical Anion

et al. 2020

Self Cite

View full text Add to dashboard Cite

The treatment of malignant cells that are deficient in oxygen due to the insufficient flow of blood is often seen as a major hindrance in radiotherapy. Such cells become radio-resistant because molecular oxygen, the natural and best radio-sensitizer, is depleted. Hence, to compensate this deficiency in oxygen, there is a need for agents that enhance radiation-induced damage of cells (radio-sensitizers) in a manner that normal cells are least affected. Simultaneously, agents capable of showing activity under hypoxic conditions are known as hypoxic cytotoxins that selectively and preferably destroy cells under hypoxic environments. 5-Nitroimidazoles fit both definitions. Their efficiency is based on their ability to generate the nitro radical anion that interacts with the strands of DNA within cells, either damaging or modifying them, leading to cell death. 5-Nitroimidazoles are important radio-pharmaceuticals (radio-sensitizers) in cancer-related treatments where the nitro radical anion has an important role. Since its generation leads to neurotoxic side effects that may be controlled through metal complex formation, this study looks at the possibility of two monomeric complexes of Ornidazole [1-chloro-3-(2-methyl-5-nitro-1 H -imidazole-1-yl)propan-2-ol] with Cu II and Zn II to be better radio-sensitizers and/or hypoxic cytotoxins than Ornidazole. The study reveals that although there is a decrease in nitro radical anion formation by complexes, such a decrease does not hamper their radio-sensitizing ability. Nucleic acid bases (thymine, cytosine, and adenine) or calf thymus DNA used as targets were irradiated with 60 Co γ rays either in the absence or presence of Ornidazole and its monomeric complexes. Radiation-induced damage of nucleic acid bases was followed by high-performance liquid chromatography (HPLC), and modification of calf thymus DNA was followed by ethidium bromide fluorescence. Studies indicate that the complexes were better in performance than Ornidazole. Cu II -ornidazole was significantly better than either Ornidazole or Zn II -ornidazole, which is attributed to certain special features of the Cu II complex; aspects like having a stable lower oxidation state enable it to participate in Fenton reactions that actively influence radio-sensitization and the ability of the complex to bind effectively to DNA.

show abstract

Section: Introductionmentioning

confidence: 73%

Section: Results and Discussionmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Radio-Sensitizing Effects of Cu^II and Zn^II Complexes of Ornidazole: Role of Nitro Radical Anion

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Effect of resveratrol on the radiosensitivity of 5‐FU in human breast cancer MCF‐7 cells

Aghamiri

Jafarpour

Zandsalimi

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

The aim of this study was to assess the efficacy of resveratrol (Res) on radiosensitivity of 5‐fluorouracil (5‐FU) in the spheroid culture of MCF‐7 breast cancer cell line using colony formation examination. Spheroids on day 9 with 300 µm diameters were treated with 20 µM resveratrol and/or 1 µM 5‐FU for one volume doubling time (VDT) (42 hours) and then irradiated with 2 Gy gamma radiation (60Co) in various groups. Then the viability of the cells and clonogenic ability were acquired by blue dye exclusion and colony formation assay, respectively. The population doubling time in the monolayer culture and the VDT of spheroid culture was 22.48 ± 0.23 hours and 42 ± 0.63 hours respectively. None of the drugs and combination of them had any effect on the viability of cells. The combination treatment of 5‐FU+Res+ radiation significantly reduced the colony formation ability of spheroid cells in comparison with each treatment alone. Our results indicated that resveratrol can significantly decrease colony number of breast cancer spheroid cells treated with 5‐FU in combination with gamma‐rays. Thus, resveratrol as a hypoxia‐inducible factor‐1‐alpha inhibitor increased the radiosensitization of breast cancer spheroid cells.

show abstract

Free radical induced activity of an anthracycline analogue and its MnII complex on biological targets through in situ electrochemical generation of semiquinone

Saha

Das

2021

Heliyon

Self Cite

View full text Add to dashboard Cite

Cytotoxicity by anthracycline antibiotics is attributed to several pathways. Important among them are formation of free-radical intermediates. However, their generation makes anthracyclines cardiotoxic which is a concern on their use as anticancer agents. Hence, any change in redox behavior that address cardiotoxicity is welcome. Modulation of redox behavior raises the fear that cytotoxicity could be compromised. Regarding the generation of free radical intermediates on anthracyclines, a lot depends on the surrounding environment (oxic or anoxic), polarity and pH of the medium. In case of anthracyclines, one-electron reduction to semiquinone or two-electron reduction to quinone-dianion are crucial both for cytotoxicity and for cardiotoxic side effects. The disproportion-comproportionation equilibria at play between quinone-dianion, free quinone and semiquinone control biological activity. Whatever is the form of reduction, semiquinones are generated as a consequence of the presence of anthracyclines and these interact with a biological target. Alizarin, a simpler anthracycline analogue and its Mn II complex were subjected to electrochemical reduction to realize what happens when anthracyclines are reduced by compounds present in cells as members of the electron transport chain. Glassy carbon electrode maintained at the pre-determined reduction potential of a compound was used for reduction of the compounds. Nucleobases and calf thymus DNA that were maintained in immediate vicinity of such radical generation were used as biological targets. Changes due to the generated species under aerated/de-aerated conditions on nucleobases and on DNA helps one to realize the process by which alizarin and its Mn II complex might affect DNA. The study reveals alizarin was more effective on nucleobases than the complex in the free radical pathway. Difference in damage caused by alizarin and the Mn II complex on DNA is comparatively less than that observed on nucleobases; the complex makes up for any inefficacy in the free radical pathway by its other attributes.

show abstract

γ radiation-induced damage of nucleic acid bases, calf thymus DNA and DNA within MCF-7 breast cancer cells by [Cu₂(OAc)₄(tnz)₂]: a potential radiosensitizer

Abstract: A Cu(ii) complex of tinidazole is more radiosensitizing than it in radiation-induced damage of nucleic acids, calf thymus DNA and DNA in MCF-7 breast cancer cells. NO2˙− was modulated to strike a balance between efficacy and toxic side effects.

Cited by 4 publications

References 43 publications

Radio-Sensitizing Effects of Cu^II and Zn^II Complexes of Ornidazole: Role of Nitro Radical Anion

Radio-Sensitizing Effects of Cu^II and Zn^II Complexes of Ornidazole: Role of Nitro Radical Anion

Effect of resveratrol on the radiosensitivity of 5‐FU in human breast cancer MCF‐7 cells

Free radical induced activity of an anthracycline analogue and its MnII complex on biological targets through in situ electrochemical generation of semiquinone

Contact Info

Product

Resources

About

γ radiation-induced damage of nucleic acid bases, calf thymus DNA and DNA within MCF-7 breast cancer cells by [Cu2(OAc)4(tnz)2]: a potential radiosensitizer

Abstract: A Cu(ii) complex of tinidazole is more radiosensitizing than it in radiation-induced damage of nucleic acids, calf thymus DNA and DNA in MCF-7 breast cancer cells. NO2˙− was modulated to strike a balance between efficacy and toxic side effects.

Cited by 4 publications

References 43 publications

Radio-Sensitizing Effects of CuII and ZnII Complexes of Ornidazole: Role of Nitro Radical Anion

Radio-Sensitizing Effects of CuII and ZnII Complexes of Ornidazole: Role of Nitro Radical Anion

Effect of resveratrol on the radiosensitivity of 5‐FU in human breast cancer MCF‐7 cells

Free radical induced activity of an anthracycline analogue and its MnII complex on biological targets through in situ electrochemical generation of semiquinone

Contact Info

Product

Resources

About

γ radiation-induced damage of nucleic acid bases, calf thymus DNA and DNA within MCF-7 breast cancer cells by [Cu₂(OAc)₄(tnz)₂]: a potential radiosensitizer

Radio-Sensitizing Effects of Cu^II and Zn^II Complexes of Ornidazole: Role of Nitro Radical Anion

Radio-Sensitizing Effects of Cu^II and Zn^II Complexes of Ornidazole: Role of Nitro Radical Anion