5-nitro-thiophene-thiosemicarbazone derivative induces cell death, cell cycle arrest, and phospho-kinase shutdown in pancreatic ductal adenocarcinoma cells

Article

作者: Albuquerque, Amanda Pinheiro de Barros ; Pitta, Maira Galdino da Rocha ; da Cruz Filho, Iranildo José ; Galdino, Lília Vieira ; Lima, Maria do Carmo Alves de ; Pereira, Michelly Cristiny ; Rêgo, Moacyr Jesus Barreto de Melo ; Silva, Bárbara de Oliveira ; Costa, Valécia de Cassia Mendonça da ; da Rosa, Michelle Melgarejo

INTRODUCTIONPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This study explores the potential of novel 5-nitro-thiophene-thiosemicarbazone derivatives as therapeutic agents for PDAC.METHODSWe evaluated the cytotoxicity of seven derivatives in peripheral blood mononuclear cells (PBMCs) and PDAC cell lines. Promising candidates (PR12 and PR17) were further analyzed for their effects on colony formation, cell cycle progression, and reactive oxygen species (ROS) production. PR17, the most promising derivative, was subjected to additional investigation, including analysis of autophagy-related genes and protein kinase inhibition.RESULTSThree derivatives (PR16, PR19, and PR20) displayed cytotoxicity towards PBMCs. PR12 reduced colony formation and G0/G1 cell cycle arrest in PDAC cells. Notably, PR17 exhibited potent activity in MIA PaCa-2 cells, inducing S-phase cell cycle arrest, downregulating autophagy genes, and inhibiting key protein kinases.CONCLUSIONPR17, a 5-nitro-thiophene-thiosemicarbazone derivative, demonstrates promising antineoplastic activity against PDAC cells by potentially modulating cell cycle progression, autophagy, and protein kinase signaling. Further studies are warranted to elucidate the detailed mechanism of action and explore its efficacy in vivo.

2024-03-01·Advanced Biology

Cytoplasmic Accumulation of Histones Induced by BET Inhibition Protects Cells from C9orf72 Poly(PR)‐Induced Cell Death

Article

作者: Wu, Yuanyuan ; Chen, Miaomiao ; Shi, Conglin ; Guo, Xiaohong ; Chen, Liuting ; Mao, Renfang ; Fan, Yihui ; Guo, Jinjing

AbstractRepeat dipeptides such as poly(proline‐arginine) (polyPR) are generated from the hexanucleotide GGGGCC repeat expansions in the C9orf72 gene. These dipeptides are often considered as the genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the study, fluorescein isothiocyanate (FITC) labeled PR20 is used to investigate PR20‐induced cell death. The findings reveal that the cell death induced by PR20 is dependent on its nuclear distribution and can be blocked by a nuclear import inhibitor called importazole. Further investigation reveals that BRD4 inhibitors, such as JQ‐1 and I‐BET762, restrict cytoplasmic localization of PR20, thereby reducing its cytotoxic effect. Mechanistically, the inhibition of BRD4 leads to an increase in the expression of numerous histones, resulting in the accumulation of histones in the cytoplasm. These cytoplasmic histones associate with PR20 and limit its distribution within the nucleus. Notably, the ectopic expression of histones alone is enough to confer protection to cells treated with PR20. In addition, phenylephrine (PE) induces cellular hypertrophy and cytoplasmic distribution of histone, which also helps protect cells from PR20‐induced cell death. The research suggests that temporarily inducing the presence of cytoplasmic histones may alleviate the neurotoxic effects of dipeptide repeat proteins.

2024-02-01·Heliyon

Sphingomonas panaciterrae PB20 increases growth, photosynthetic pigments, antioxidants, and mineral nutrient contents in spinach (Spinacia oleracea L.)

Article

作者: Sultana, Razia ; Sriti, Nurjahan ; Jashim, Asif Iqbal Ibne ; Shuvo, Sourav Biswas ; Islam, Shah Mohammad Naimul ; Ahmed, Mysha ; Rahman, Md Habibur

Plant growth promoting rhizobacteria (PGPR) have been intensively investigated in agricultural crops for decades. Nevertheless, little information is available on the application of Sphingomonas spp. as a PGPR particularly in vegetables, despite of potential plant growth promoting traits of this group. This study investigated the role of Sphingomonas panaciterrae (PB20) on growth and nutritional profile of spinach applied through seed priming (SP), soil drenching (SD), foliar application (FA), and bacterial culture filtrate foliar (BCF) applications. The results showed that, depending on different methods of application, PB20 significantly increased plant height (19.57-65.65 %), fresh weight (7.26-37.41 %), total chlorophyll (71.14-192.54 %), carotenoid (67.10-211.67 %) antioxidant (55.99-207.04), vitamin C (8.1-94.6 %) and protein content (6.7-21.5 %) compared to control in the edible part of spinach. Among the mineral nutrients, root nitrogen (N) showed greater response to bacterial application (18.65%-46.15 % increase over control) than shoot nitrogen (6.70%-21.52 % increased over control). Likewise, in all methods of application, phosphorus (P) content showed significant increase over control both in root (42.79-78.48 %) and in shoot (3.57-27.0 %). Seed priming and foliar application of PB20 increased the shoot calcium (Ca) content compared to control. BCF foliar application yielded maximum magnesium (Mg), iron (Fe) and zinc (Zn) in shoot. However, seed priming resulted in maximum Fe in root. Overall, seed priming outperformed in growth, vitamin C, antioxidants, N and P uptake, while BCF foliar application resulted in better uptake of several nutrients. Multivariate analysis validated the positive association of most of the growth parameters with SP while several nutrients with FA and BCF. Based on the findings it is evident that this rhizobacteria PB20 has the potentiality to be applied as a biofertilizer to produce nutrient-enriched spinach with an improved yield. Farmers can conveniently incorporate PR20 through seed priming before planting of spinach, with additional benefits through foliar spray.

100 项与 PR020 相关的药物交易

登录后查看更多信息