Daidzein-directed methionine γ-lyase in enzyme prodrug therapy against breast cancer

Thiosulfinates in situ formed by “pharmacological pair” C115H methionine γ-lyase/S-(allyl/alkyl)-l-cysteine sulfoxides possess cytotoxic activity against various malignant cell lines. To investigate in vivo antitumor activity of thiosulfinates generated directly at the surface of tumor cells, a chem...

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Bibliographic Details
Published in:Biochimie 2022-10, Vol.201, p.177-183
Main Authors: Morozova, E., Abo Qoura, L., Anufrieva, N., Koval, V., Lesnova, E., Kushch, A., Kulikova, V., Revtovich, S., Pokrovsky, V.S., Demidkina, T.
Format: Article
Language:English
Subjects:
Breast carcinoma
Daidzein
Enzyme prodrug therapy
Methionine γ-lyase
Targeted delivery
Thiosulfinates
Xenografts
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Summary:Thiosulfinates in situ formed by “pharmacological pair” C115H methionine γ-lyase/S-(allyl/alkyl)-l-cysteine sulfoxides possess cytotoxic activity against various malignant cell lines. To investigate in vivo antitumor activity of thiosulfinates generated directly at the surface of tumor cells, a chemical conjugate between Clostridium novyi C115H methionine γ-lyase (C115H MGL) and isoflavone daidzein was prepared. The binding of conjugate (C115H-Dz) to various breast cancer cell lines was demonstrated, as well as its cytotoxicity in the presence of S-(allyl/alkyl)-l-cysteine sulfoxides. The most promising among thiosulfinates was dipropyl thiosulfinate (IC50 
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2022.05.007