FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties

  1. Canerina-Amaro, Ana
  2. Mesa-Herrera, Fátima 1
  3. Lobo, Fernando 1
  4. Lahoz, Fernando 1
  5. Hernández, Dácil
  6. Marín, Raquel 1
  7. Estévez-Braun, Ana 1
  8. Díaz, Mario
  9. Valdés-Baizabal, Catalina 1
  10. Soler, Kevin 1
  11. Boto, Alicia
  12. Amesty, Ángel 1
  1. 1 Universidad de La Laguna
    info

    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

Revue:
International Journal of Molecular Sciences

ISSN: 1422-0067

Année de publication: 2021

Volumen: 22

Número: 10

Pages: 5339

Type: Article

DOI: 10.3390/IJMS22105339 GOOGLE SCHOLAR lock_openAccès ouvert editor
Texte intégral de l'auteur: lock_openAccès ouvert editor

Résumé

Tamoxifen is the most widely used selective modulator of estrogen receptors (SERM) and the first strategy as coadjuvant therapy for the treatment of estrogen-receptor (ER) positive breast cancer worldwide. In spite of such success, tamoxifen is not devoid of undesirable effects, the most life-threatening reported so far affecting uterine tissues. Indeed, tamoxifen treatment is discouraged in women under risk of uterine cancers. Recent molecular design efforts have endeavoured the development of tamoxifen derivatives with antiestrogen properties but lacking agonistic uterine tropism. One of this is FLTX2, formed by the covalent binding of tamoxifen as ER binding core, 7-nitrobenzofurazan (NBD) as the florescent dye, and Rose Bengal (RB) as source for reactive oxygen species. Our analyses demonstrate (1) FLTX2 is endowed with similar antiestrogen potency as tamoxifen and its predecessor FLTX1, (2) shows a strong absorption in the blue spectral range, associated to the NBD moiety, which efficiently transfers the excitation energy to RB through intramolecular FRET mechanism, (3) generates superoxide anions in a concentration- and irradiation time-dependent process, and (4) Induces concentration- and time-dependent MCF7 apoptotic cell death. These properties make FLTX2 a very promising candidate to lead a novel generation of SERMs with the endogenous capacity to promote breast tumour cell death in situ by photosensitization.

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