RESUMO
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four benzo[f]indole-4,9-dione derivatives reduce TNBC cell viability by reactive oxygen species (ROS) accumulation stress in vitro. Further analyses showed that LACBio1, LACBio2, LACBio3 and LACBio4 exert cytotoxic effects on MDA-MB 231 cancer cell line by inducing the intrinsic apoptosis pathway, activating caspase 9 and Bax/Bcl-2 pathway in vitro. These results provide evidence that these new four benzo[f]indole-4,9-dione derivatives could be potential therapeutic agents against TNBC by promoting ROS stress-mediated apoptosis through intrinsic-pathway caspase activation.
Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Citotoxinas , Indóis , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Feminino , Humanos , Indóis/síntese química , Indóis/química , Indóis/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists andneuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in termsof functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mousemodel of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of theextraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal andmesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 andcompression of the spinal cord with a vascular clip for 1 min. The cells were transplanted 7 days or 28 days afterthe lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. Weperformed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, andultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better whitematterpreservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissueorganization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, inaddition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. Wealso demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functionalanalysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCsmay be feasible candidates for therapeutic intervention after SCI and central nervous system disorders inhumans.