RESUMO
According to estimates, cancer will be the leading cause of death globally in 2022, accounting for 9.6 million deaths. At present, the three main therapeutic modalities utilized to treat cancer are radiation therapy, chemotherapy, and surgery. However, during treatment, tumor cells resistant to chemotherapy may arise. Drug resistance remains a major oppose since it often leads to therapeutic failure. Furthermore, the term "acquired drug resistance" describes the situation where tumor cells already display drug resistance before undergoing chemotherapy. However, little is still known about the basic mechanisms underlying chemotherapy-induced drug resistance. The development of new technologies and bioinformatics has led to the discovery of additional genes associated with drug resistance. Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been linked to an increased risk of cancer, according to a growing body of research. Apart from biological functions associated with cell division, development, pluripotency, and cell cycle, lncRNA PVT1 contributes significantly to the regulation of various aspects of genome function, such as transcription, splicing, and epigenetics. The article will address the mechanism by which lncRNA PVT1 influences drug resistance in cancer cells.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Neoplasias/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
In this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)-thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by the Pt(II)-thiocarbohydrazone complex was associated with cell cycle arrest at the G0/G1 phase. These findings suggest that the target complex inhibited the proliferation of Caov-3 and HT-29 cells, resulting in the arrest of the cell cycle and induction of apoptosis via the stimulation of the p53 and caspase-8 pathways. The present data suggests that the Pt(II)-thiocarbohydrazone complex could also be a promising chemotherapeutic agent for other types of cancer cells.
RESUMO
A new thiosemicarbazone (LH2) derived from indole-7-carbaldehyde was synthesized and reacted with Zn(II), Cd(II), Pd(II) and Pt(II) salts. The reactions with zinc and cadmium salts in 2 : 1 (ligand-metal) molar ratio afforded complexes of the type MX2(LH2)2, (X = Cl, Br or OAc), in which the thiosemicarbazone acts as a neutral S-monodentate ligand. In the presence of potassium hydroxide, the reaction of LH2 with ZnBr2 resulted in deprotonation of the thiosemicarbazone at the hydrazine and indole nitrogens to form Zn(L)(CH3OH). The reaction of LH2 with K2PdCl4 in the presence of triethylamine, afforded Pd(L)(LH2) which contains two thiosemicarbazone ligands: one being dianionic N,N,S-tridentate while the other one is neutral S-monodentate. When PdCl2(PPh3)2 was used as the Pd(II) ion source, Pd(L)(PPh3) was obtained. In a similar manner, the analogous platinum complex, Pt(L)(PPh3), was synthesized. The thiosemicarbazone in the latter two complexes behaves in a dianionic N,N,S-tridentate fashion. The platinum complex was found to have significant cytotoxicity toward four cancer cells lines, namely MDA-MB-231, MCF-7, HT-29, and HCT-116 but not toward the normal liver WRL-68 cell line. The apoptosis-inducing properties of the Pt complex was explored through fluorescence microscopy visualization, DNA fragmentation analysis and propidium iodide flow cytometry.