RESUMO
PURPOSE: In contrast to hormone receptor driven breast cancer, patients presenting with triple-negative breast cancer (TNBC) often have limited drug treatment options. Efavirenz, a non-nucleoside reverse transcriptase (RT) inhibitor targets abnormally overexpressed long interspersed nuclear element 1 (LINE-1) RT and has been shown to be a promising anticancer agent for treating prostate and pancreatic cancers. However, its effectiveness in treating patients with TNBC has not been comprehensively examined. METHODS: In this study, the effect of Efavirenz on several TNBC cell lines was investigated by examining several cellular characteristics including viability, cell division and death, changes in cell morphology as well as the expression of LINE-1. RESULTS: The results show that in a range of TNBC cell lines, Efavirenz causes cell death, retards cell proliferation and changes cell morphology to an epithelial-like phenotype. In addition, it is the first time that a whole-genome RNA sequence analysis has identified the fatty acid metabolism pathway as a key regulator in this Efavirenz-induced anticancer process. CONCLUSION: In summary, we propose Efavirenz is a potential anti-TNBC drug and that its mode of action can be linked to the fatty acid metabolism pathway.
Assuntos
Alcinos/uso terapêutico , Antineoplásicos/uso terapêutico , Benzoxazinas/uso terapêutico , Ciclopropanos/uso terapêutico , Elementos Nucleotídeos Longos e Dispersos , Inibidores da Transcriptase Reversa/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Morte Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Regulação para Baixo , Ácidos Graxos/metabolismo , Feminino , Humanos , Fenótipo , Transcriptoma , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Human alpha(1)-acid glycoprotein (AGP) or orosomucoid (ORM) is a major acute phase protein that is thought to play a crucial role in maintaining homeostasis. Human AGP is the product of a cluster of at least two adjacent genes located on HSA chromosome 9. Using a range of restriction endonucleases we have investigated DNA variation at the locus encoding the AGP genes in a group of healthy Caucasians. Polymorphisms were identified using BamHI, EcoRI, BglII, PvuII, HindIII, TaqI and MspI. Nonrandom associations were found between the BamHI, EcoRI and BglII RFLPs. The RFLPs detected with PvuII, TaqI and MspI were all located in exon 6 of both AGP genes. The duplication of an AGP gene was observed in 11 of the individuals studied and was in linkage disequilibrium with the TaqI RFLP. The identification and characterization of these polymorphisms should prove useful for other population and forensic studies
Assuntos
Humanos , DNA , População Branca , Orosomucoide/genética , Alelos , Southern Blotting , DNA , Desequilíbrio de Ligação/genética , Frequência do Gene , Ligação Genética , Genes Duplicados/genética , LinhagemRESUMO
The distribution of the three previously reported alleles, with normal products at the factor XIII A subunit structural locus, FXIIIA*1, FXIIIA*2 and FXIIIA*4 has been studied in populations from the region extending from the Indonesian archipelago through Papua New Guinea, Australia and New Zealand to the Pacific Islands of Micronesia, Melanesia and Polynesia. In addition a population from the Caspian Littoral of Iran and a population of South American Indians were studied. The FXIIIA*1 and FXIIIA*2 alleles were polymorphic in all populations studied. The distribution of the FXIIIA*4 allele suggests that it may be a Melanesian marker.