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Phenotype-based discovery of a HeLa-specific cytotoxic molecule that downregulates HPV-mediated signaling pathways via oxidative damage
- Source :
- Organicbiomolecular chemistry. 17(31)
- Publication Year :
- 2019
-
Abstract
- Selective bioactive compounds have emerged as major players in chemical biology for their potential in disrupting diverse biological pathways with minimal adverse effects. Using phenotypic screening, we identified an anti-cancer agent, SB2001, with a highly specific cytotoxicity toward HeLa human cervical cancer cells. The subsequent mechanistic study revealed that SB2001 induced apoptotic cell death through restoring p53 function and suppressed the human papillomavirus (HPV)-mediated oncoprotein signaling pathway via oxidative damage in HeLa cells. SB2001 also selectively induced HeLa-specific tumor regression without any adverse effects in an in vivo tumor xenograft model, demonstrating its potential as a promising chemical probe.
- Subjects :
- 0301 basic medicine
Male
Programmed cell death
Cell Survival
Pyridines
Phenotypic screening
Chemical biology
Down-Regulation
Antineoplastic Agents
010402 general chemistry
01 natural sciences
Biochemistry
Heterocyclic Compounds, 2-Ring
Biological pathway
HeLa
03 medical and health sciences
Mice
Structure-Activity Relationship
Drug Discovery
Tumor Cells, Cultured
Animals
Humans
Physical and Theoretical Chemistry
Cytotoxicity
Papillomaviridae
Cell Proliferation
Mice, Inbred ICR
biology
Dose-Response Relationship, Drug
Molecular Structure
Chemistry
Organic Chemistry
Cell Cycle
Optical Imaging
Neoplasms, Experimental
biology.organism_classification
0104 chemical sciences
Oxidative Stress
030104 developmental biology
Phenotype
Apoptosis
Cancer research
Pyrazoles
Signal transduction
Drug Screening Assays, Antitumor
Signal Transduction
Subjects
Details
- ISSN :
- 14770539
- Volume :
- 17
- Issue :
- 31
- Database :
- OpenAIRE
- Journal :
- Organicbiomolecular chemistry
- Accession number :
- edsair.doi.dedup.....902077b89be310f695c7c03538b0c2e4