Year: 2024
Type: article
Abstract: Cancer is a leading cause of death, so continuous efforts into cancer therapy are imperative. In tumor cells, telomerase and oncogene activity are key points for uncontrolled cell growth. Targeting these processes with ligands that inhibit telomerase and/or reduce oncogene expression has been identified as a promising cancer therapy. This study evaluated the selectivity and affinity of the silverII complex of 5,10,15,20-tetrakis(N-methyl-4-pyridinium)porphyrin (AgTMPyP) to stabilize DNA sequences capable of forming G4 structures mimicking the telomeric and oncogene regions, using spectroscopic, biochemical methods and in vitro assays. The tetracationic silver complex was compared with the free base, H2TMPyP, and the zincII complex, ZnTMPyP. The results obtained from UV-Vis and fluorescence methods pointed to a great affinity and good selectivity of AgTMPyP to G4 structures, especially for the oncogene MYC. In general, an increase in the ability of the studied ligands for 1O2 generation when interacting with oncogenic and telomeric G4 sequences was found. The results of the PCR stop assays proved that AgTMPyP has the ability to inhibit Taq polymerase. Additionally, in vitro assays demonstrated that the silverII complex exhibits low cytotoxicity against HaCaT— an immortalized, non-tumorigenic, skin keratinocytes cell line—and, although nonexclusive, AgTMPyP shows nuclear co-localization.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,296
Awards: G1169335522, G1240268737, G138060719, G1392191582, G1483381719, G1509028180, G1522114529, G1690109813, G1977608718, G2012127377, G2025597285, G2149047050, G2219685250, G2339299466, G2346795057, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, G2564222079, G2573174479, G2673245850, G2734793695, G2736865772, G2756637201, G2783038177, G2814222956, Centro de Estudos do Ambiente e do Mar, G3127682330, G3215331688, G3226779992, G3286926264, G3307806965, G332082475, G3451667969, G3534458110, G3729557023, G375633160, G384841507, Centro de Estudos do Ambiente e do Mar, G4046065984, G4090066734, G4232193333, G4378797157, G4897246272, G5389921940, G5454278309, G567200461, Centro de Estudos do Ambiente e do Mar, G5868090805, G6113984419, G6119126181, G6463117426, G6872244839, G6997658380, G7334419788, G7441985484, G745763725, G7501588509, G7665809008, G7786427436, G8173101688, G8213652065, G824076568, G8479097375, Centro de Estudos do Ambiente e do Mar, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, G8963217260
OpenAlex ID: W4405511719