Anticancer effect of a pyrrole-imidazole polyamide-triphenylphosphonium conjugate selectively targeting a common mitochondrial DNA cancer risk variant in cervical cancer cells

Menée à l'aide de lignées cellulaires, de cellules cancéreuses issues de patientes atteintes d'un carcinome à cellules claires du col utérin et d'une xénogreffe sur un modèle murin, cette étude met en évidence l'effet antitumoral d'un conjugué polyamide pyrrole-imidazole-triphénylphosphonium ciblant le variant 8860A>G du gène ATP6 de l'ADN mitochondrial

Résumé en anglais

Abstract Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860A>G) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers. This article is protected by copyright. All rights reserved.