Correction: Suprafenacine, an Indazole-Hydrazide Agent, Targets Cancer Cells Through Microtubule Destabilization

Autor: Lin Feng, Nagakumar Bharatham, Amaravadhi Harikishore, Le Nguyen Thanh, Xue-Wei Liu, Souvik Chattopadhaya, Quoc Toan Nguyen, Yan Zhao, Chuan Bian Lim, Ho Sup Yoon, Bo-Hwa Choi, Ravi Prakash Reddy Nanga
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Cancer Treatment
lcsh:Medicine
Apoptosis
PC12 Cells
Biochemistry
Microtubules
Mice
chemistry.chemical_compound
Cell Signaling
Molecular Cell Biology
Basic Cancer Research
Drug Discovery
Medicine and Health Sciences
Inner mitochondrial membrane
lcsh:Science
Cytoskeleton
Apoptotic Signaling
Membrane Potential
Mitochondrial
Membrane potential
Multidisciplinary
medicine.diagnostic_test
Cell Death
Cell biology
G2 Phase Cell Cycle Checkpoints
Cell Motility
Hydrazines
Oncology
Cell Processes
Phosphorylation
Cellular Structures and Organelles
Protein Binding
Research Article
Biotechnology
Signal Transduction
Indazoles
Drug Research and Development
Molecular Sequence Data
Biophysics
Antineoplastic Agents
Cell Growth
Flow cytometry
Small Molecule Libraries
Microtubule
Chemical Biology
medicine
Animals
Humans
Amino Acid Sequence
Pharmacology
Indazole
Binding Sites
lcsh:R
Correction
Biology and Life Sciences
Cell Biology
Rats
chemistry
Small Molecules
Cancer cell
lcsh:Q
Clinical Medicine
Colchicine
HeLa Cells
Zdroj: PLoS ONE, Vol 13, Iss 7, p e0201149 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3. Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our results suggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents.
Databáze: OpenAIRE
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