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Caffeine Enhances the Toxicity of Platinum-Based Drugs at the Molecular Level Even Outside of the Intracellular Environment: A Single-Molecule Force Spectroscopy Study.
de Oliveira, Rayane M; Moura, Tiago A; Rocha, Márcio S.
Afiliação
  • de Oliveira RM; Departamento de Física, Universidade Federal de Viçosa, Viçosa 36570-900, Minas Gerais, Brazil.
  • Moura TA; Departamento de Física, Universidade Federal de Viçosa, Viçosa 36570-900, Minas Gerais, Brazil.
  • Rocha MS; Departamento de Física, Universidade Federal de Viçosa, Viçosa 36570-900, Minas Gerais, Brazil.
J Phys Chem B ; 126(17): 3291-3299, 2022 05 05.
Article em En | MEDLINE | ID: mdl-35442688
It is well reported in the literature that caffeine, the most consumed alkaloid around the world, enhances the anticancer effects of the drug cisplatin by inhibiting DNA repair by the cellular machinery. Here, we perform single-molecule force spectroscopy assays with optical tweezers to show that caffeine enhances the toxicity not only of cisplatin but also of various different platinum-based drugs already at the molecular level, using samples containing only double-stranded (ds)DNA, platinum drugs, and the alkaloid in a simple phosphate buffer, that is, completely out of the complex environment found inside real living cells. In fact, our results show that caffeine acts as an allosteric catalyst which increases the effective equilibrium binding constant between DNA and the platinum drugs, also interfering in the cooperativity of the binding reactions. To the best of our knowledge, this is the first time that such a property of caffeine was demonstrated and characterized from a pure physicochemical perspective, outside the cellular environment. Thus, the present work provides new insights into the use of this alkaloid for current chemotherapeutic applications.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Antineoplásicos Idioma: En Revista: J Phys Chem B Assunto da revista: QUIMICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Antineoplásicos Idioma: En Revista: J Phys Chem B Assunto da revista: QUIMICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos