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Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide

Borges, Gabriel Silva Marques ; Sicard, Pierre ; de Mello Gomides Loures, Cristina ; Evangelista, Fernanda Gontijo Cristina ; Sales, Camila Campos ; de Paula Sabino, Adriano ; Fernandes, Christian ; Ferreira, Lucas Antônio Miranda ; Richard, Sylvain

AAPS PharmSciTech, 2023-03, Vol.24 (3), p.79-79, Article 79 [Periódico revisado por pares]

Cham: Springer International Publishing

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Título:
Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide
Autor: Borges, Gabriel Silva Marques ; Sicard, Pierre ; de Mello Gomides Loures, Cristina ; Evangelista, Fernanda Gontijo Cristina ; Sales, Camila Campos ; de Paula Sabino, Adriano ; Fernandes, Christian ; Ferreira, Lucas Antônio Miranda ; Richard, Sylvain
Assuntos: Animals ; Arsenic Trioxide - pharmacology ; Arsenic Trioxide - therapeutic use ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Electrocardiography ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - metabolism ; Life Sciences ; Mice ; Oxides - pharmacology ; Oxides - therapeutic use ; Pharmacology/Toxicology ; Pharmacy ; Research Article ; Tocotrienols - therapeutic use ; Tretinoin - pharmacology ; Tretinoin - therapeutic use
É parte de: AAPS PharmSciTech, 2023-03, Vol.24 (3), p.79-79, Article 79
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: All- trans retinoic acid and arsenic trioxide are the leading choices for the treatment of acute promyelocytic leukemia. Notwithstanding the impressive differentiative properties of all- trans retinoic acid and the apoptotic properties of arsenic trioxide, some problems still occur in acute promyelocytic leukemia treatment. These problems are due to patients’ relapses, mainly related to changes in the ligand-binding domain of RARα (retinoic acid receptor α) and the cardiotoxic effects caused by arsenic trioxide. We previously developed a self-nanoemulsifying drug delivery system enriched with tocotrienols to deliver all- trans retinoic acid (SNEDDS-TRF-ATRA). Herein, we have evaluated if tocotrienols can help revert ATRA resistance in an APL cell line (NB4-R2 compared to sensitive NB4 cells) and mitigate the cardiotoxic effects of arsenic trioxide in a murine model. SNEDDS-TRF-ATRA enhanced all- trans retinoic acid cytotoxicity in NB4-R2 (resistant) cells but not in NB4 (sensitive) cells. Moreover, SNEDDS-TRF-ATRA did not significantly change the differentiative properties of all - trans retinoic acid in both NB4 and NB4-R2 cells. Combined administration of SNEDDS-TRF-ATRA and arsenic trioxide could revert QTc interval prolongation caused by ATO but evoked other electrocardiogram alterations in mice, such as T wave flattening. Therefore, SNEDDS-TRF-ATRA may enhance the antileukemic properties of all - trans retinoic acid but may influence ECG changes caused by arsenic trioxide administration. Graphical Abstract SNEDDS-TRF-ATRA presents cytotoxicity in resistant APL cells (NB4-R2). Combined administration of ATO and SNEDDS-TRF-ATRA in mice prevented the prolongation of the QTc interval caused by ATO but evoked ECG abnormalities such as T wave flattening.
Editor: Cham: Springer International Publishing
Idioma: Inglês

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Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide

Borges, Gabriel Silva Marques ; Sicard, Pierre ; de Mello Gomides Loures, Cristina ; Evangelista, Fernanda Gontijo Cristina ; Sales, Camila Campos ; de Paula Sabino, Adriano ; Fernandes, Christian ; Ferreira, Lucas Antônio Miranda ; Richard, Sylvain

Cham: Springer International Publishing

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