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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Olivomycin induces tumor cell apoptosis and suppresses p53-induced transcription
V S Simonova1, A V Samusenko, N A Filippova
1Institute of Carcinogenesis, N. N. Blokhin Oncological Research Center, Russian Academy of Medical Sciences, Russia.
Abstract:
Olivomycin (DNA-binding antibiotic) in nanomolar concentrations induces apoptosis of human tumor cells and inhibits p53-dependent transcription of the reporter gene (basal and induced by antitumor drugs). Olivomycin aglycon induces no cytotoxicity and does not block transcription.
Insights
Olivomycin, a DNA-binding antibiotic, triggers cancer cell death (apoptosis) at low concentrations. It also blocks p53-dependent gene transcription, a key process in tumor suppression.
Area of Science:
- Molecular Biology
- Pharmacology
- Cancer Research
Background:
- Olivomycin is a DNA-binding antibiotic with known biological activity.
- The role of p53-dependent transcription in tumor cell response to drugs is critical.
- Understanding the specific mechanisms of action for antibiotics like Olivomycin is important for therapeutic development.
Purpose of the Study:
- To investigate the effects of Olivomycin on human tumor cells.
- To determine Olivomycin's impact on p53-dependent gene transcription.
- To differentiate the effects of Olivomycin from its aglycon.
Main Methods:
- Treatment of human tumor cells with Olivomycin and its aglycon.
- Assessment of cytotoxicity using cell viability assays.
- Measurement of reporter gene transcription, both basal and drug-induced, in a p53-dependent manner.
Main Results:
- Olivomycin induced apoptosis in human tumor cells at nanomolar concentrations.
- Olivomycin inhibited p53-dependent reporter gene transcription, affecting both basal and induced states.
- Olivomycin aglycon showed no significant cytotoxicity and did not inhibit transcription.
Conclusions:
- Olivomycin exhibits potent anti-tumor activity through apoptosis induction.
- The DNA-binding and transcriptional inhibitory effects of Olivomycin are linked to its cytotoxic action.
- The aglycon component of Olivomycin lacks the cytotoxic and transcriptional inhibitory properties, suggesting the intact molecule is required for these effects.
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