RESUMO
A cationic BODIPY-based G-quadruplex-selective stabiliser is developed and shown to decrease cancer cell migration-invasion up to 90%. The expression of critical genes (HIF1α, VIM, CDH1) related to metastasis is modulated. The stabiliser reprograms hypoxia-adaptive metabolism and an 1.82-fold increase in O2 consumption, enabling back-to-normal switching of energy metabolism, is observed. Stabilisers with a strong G-quadruplex affinity (0.38 µM Kd) significantly contribute to small molecule anti-cancer approaches.
Assuntos
Quadruplex G , Neoplasias , Compostos de Boro/farmacologiaRESUMO
In the research, the modulation of gene expression with a novel G-quadruplex stabiliser was analysed. Activation by the removal of bulky hypoxia-responsive substituent enhances G-quadruplex stabilisation. Hypoxic MCF7 cells incubated with the stabiliser displayed significant downregulation of oncogenes c-myc, bcl-2, and hif-1α. This study presents the first hypoxia-activatable G-quadruplex stabilization and transcriptional regulation.
Assuntos
Hipóxia , Neoplasias , Humanos , Hipóxia Celular , Linhagem Celular Tumoral , Regulação para Baixo , Expressão Gênica , Regulação da Expressão Gênica , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células MCF-7RESUMO
Cell-selective activity regulation of therapeutics is necessary for efficient personalized treatments with minimal off-target effects. Here, the first example of a structurally simple, pyridinium BODIPY-based, tyrosinase activatable photosensitizer is developed and the cytotoxic singlet oxygen generation capacity is analysed. Singlet oxygen quantum yields of active and inactive forms are determined to be 0.64 and 0.02, respectively. Selective photo-induced cell death in mouse melanoma cells over mammary and hepatocellular carcinoma proved the potential of the photosensitizer in tissue-selective therapies.
