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Updated: Jul 15, 2026
08:47
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Caspase activation by anticancer drugs: the caspase storm
Zhimin Tao1, Jerry Goodisman, Harvey S Penefsky
1Department of Chemistry, Syracuse University, 1-014 CST, Syracuse, New York 13244, USA.
Molecular Pharmaceutics
|April 19, 2007
Summary
Anticancer drugs trigger cellular caspase activation and impair respiration, with varying timelines. Mitochondria are rapidly targeted by caspases, impacting cellular ATP levels.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Anticancer drugs induce apoptosis through various mechanisms.
- Caspase activation is a key event in programmed cell death.
- Cellular respiration is crucial for energy production and cell viability.
Purpose of the Study:
- To measure the time-dependence of caspase activation induced by anticancer drugs.
- To compare caspase activation kinetics with changes in cellular respiration.
- To investigate the role of topoisomerase-II in drug-induced caspase activation.
Main Methods:
- Utilized fluorogenic substrate Ac-DEVD-AFC for intracellular caspase activity measurement.
- Employed High-Performance Liquid Chromatography (HPLC) for AFC detection.
- Assessed cellular respiration and ATP levels.
- Used pancaspase inhibitor benzyloxycarbonyl-val-ala-asp-fluoromethylketone to confirm caspase involvement.
Main Results:
- Dactinomycin and doxorubicin induced caspase activation within 2 hours, peaking around 6-8 hours.
- Doxorubicin-induced caspase activation was delayed in topoisomerase-II deficient cells.
- Cisplatin induced noticeable caspase activity after approximately 14 hours.
- All tested drugs impaired cellular respiration and decreased ATP levels, correlating with caspase activation.
Conclusions:
- Anticancer drugs exhibit distinct time-dependent caspase activation profiles.
- Topoisomerase-II plays a critical role in doxorubicin-induced cytotoxicity.
- Mitochondria are rapidly targeted by activated caspases, leading to impaired cellular respiration and ATP depletion.
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