A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions DOI Creative Commons
Siyi He, Luis Fernando Delgadillo-Silva, Guy A. Rutter

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 15, 2023

Abstract Inducing apoptosis in different types of cancer cells is an effective therapeutic strategy. However, the success existing chemotherapeutics can be compromised by tumor cell resistance and systemic off-target effects. Therefore, discovery pro-apoptotic compounds with minimal side-effects crucial. 14-3-3 proteins are molecular scaffolds that serve as important regulators survival. Our previous study demonstrated 14-3-3ζ sequester BAD, a member BCL-2 protein family, cytoplasm prevent its translocation to mitochondria inhibit induction apoptosis. Despite being critical mechanism survival, it unclear whether disrupting protein:BAD interactions could harnessed chemotherapeutic approach. Herein, we established BRET-based high-throughput drug screening approach (Z’-score= 0.52) capable identifying molecules disrupt 14-3-3ζBAD interactions. An FDA-approved library containing 1971 was used for screening, capacity identified hits induce death examined NIH3T3-fibroblasts colorectal lines, HT-29 Caco-2. vitro results suggest terfenadine, penfluridol, lomitapide potentially repurposed treating cancer. Moreover, our method demonstrates feasibility agents applied towards conditions where aberrant growth or function key determinants disease pathogenesis.

Language: Английский

Preparation and Evaluation of Microbial Resistance of Nortriptyline Mouthwash Based on Pharmaceutical Pharmacopoeia Standards with the Aim of Application in Oral Mucositis DOI

Taher Sadeghian,

Saeideh Allahyari

Deleted Journal, Journal Year: 2024, Volume and Issue: 24(1), P. 19 - 34

Published: April 1, 2024

Language: Английский

Citations

0
A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions DOI Creative Commons
Gareth E. Lim, Siyi He, Daniel Meister

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract Selectively inducing apoptosis in cancer cells is an effective therapeutic strategy, but the reality of success existing chemotherapeutics compromised by emergent tumor cell resistance and systemic off-target effects. Therefore, discovery new classes pro-apoptotic compounds with minimal side-effects remains urgent need. 14-3-3 proteins are molecular scaffolds that serve as important regulators survival. Our previous study demonstrated 14-3-3ζ can sequester BAD, a member BCL-2 protein family, cytoplasm to inhibit induction apoptosis. Despite being critical mechanism survival, it unclear whether disrupting protein:BAD interactions could be harnessed chemotherapeutic approach. Herein, we established BRET-based, high-throughput drug screening approach (Z’-score = 0.52) capable identifying molecules disrupt 14-3-3ζ:BAD interactions. An FDA-approved library containing 1971 was used for screening, capacity identified hits induce death examined NIH-3T3 fibroblasts colorectal lines, HT-29 Caco-2. in vitro results suggest terfenadine, penfluridol, lomitapide potentially repurposed treating cancer. silico structural analysis, validated grounding experimental data, provides insight into specific highlights proposed binding modes further modified refine affinity selectivity hits. This multi-modal method demonstrates feasibility agents applied towards conditions where aberrant growth or function key determinants disease pathogenesis.

Language: Английский

Citations

0
Comparative Efficacy of Chlorhexidine and Fluorine Total Mouthwashes Against Candida albicans and Streptococcus sanguinis DOI Open Access

Kasra Ghafari,

Reyhaneh Shoorgashti, Simin Lesan

et al.

Archives of Clinical Infectious Diseases, Journal Year: 2024, Volume and Issue: 19(5)

Published: Oct. 28, 2024

Background: Candidiasis, primarily caused by Candida albicans (C. albicans), is the most common fungal and opportunistic infection of oral cavity. Streptococcussanguinis (S. sanguinis) also plays a significant role in infectious endocarditis various dental diseases. Objectives: This study aimed to evaluate effects chlorhexidine (CHX) fluorine total (FT) mouthwashes on C.albicans S.sanguinis. Methods: In this laboratory-based experimental study, 40 samples were analyzed. A 0.5 McFarland standard concentration S.sanguinis (1.5 × 108 CFU/mL) C. (0.5 106 cultured using spread method 18 blood agar plates Sabouraud Dextrose Agar (SDA) plates, respectively. The inhibition zones measured compared between CHX FT treatments. inclusion criteria specified from individuals aged - 65, with exclusions for those who had taken antibiotics within past month. Data analyzed SPSS version 25, statistical significance determined t-tests. Results: mean zone was 2.41 ± 0.17 mm 1.47 0.08 FT. For S. sanguinis, 17.96 0.11 12.13 0.18 Chlorhexidine showed significantly greater inhibitory than (P < 0.001). Conclusions: demonstrated superior efficacy over against both microorganisms, indicating that may be more effective therapeutic use controlling sanguinis infections.

Language: Английский

Citations

0
A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions DOI Creative Commons
Siyi He, Luis Fernando Delgadillo-Silva, Guy A. Rutter

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 15, 2023

Abstract Inducing apoptosis in different types of cancer cells is an effective therapeutic strategy. However, the success existing chemotherapeutics can be compromised by tumor cell resistance and systemic off-target effects. Therefore, discovery pro-apoptotic compounds with minimal side-effects crucial. 14-3-3 proteins are molecular scaffolds that serve as important regulators survival. Our previous study demonstrated 14-3-3ζ sequester BAD, a member BCL-2 protein family, cytoplasm prevent its translocation to mitochondria inhibit induction apoptosis. Despite being critical mechanism survival, it unclear whether disrupting protein:BAD interactions could harnessed chemotherapeutic approach. Herein, we established BRET-based high-throughput drug screening approach (Z’-score= 0.52) capable identifying molecules disrupt 14-3-3ζBAD interactions. An FDA-approved library containing 1971 was used for screening, capacity identified hits induce death examined NIH3T3-fibroblasts colorectal lines, HT-29 Caco-2. vitro results suggest terfenadine, penfluridol, lomitapide potentially repurposed treating cancer. Moreover, our method demonstrates feasibility agents applied towards conditions where aberrant growth or function key determinants disease pathogenesis.

Language: Английский

Citations

0