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Published on: January 7, 2013
Rokitamycin induces a mitochondrial defect and caspase-dependent apoptosis in human T-cell leukemia Jurkat cells
Masayuki Fukui1, Yukitoshi Nagahara, Yoshiaki Nishio
1Department of Pharmacology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Abstract:
Macrolides are a well-known family of oral antibiotics whose antibacterial spectrum of activity covers most relevant bacterial species responsible for respiratory infectious disease. In recent years, it has been reported that macrolides have not only bactericidal activity but also direct immunomodulating activity in mammals. In this study, we observed new physiological activity of macrolides and examined whether various macrolides induce apoptosis in human leukemia cell lines. We investigated the effects of 13 different macrolides on the viability of Jurkat and HL-60 cells. Among all the macrolides used in this study, rokitamycin, a semisynthetic macrolide with a 16-member ring, effectively induced cell death. Rokitamycin induced DNA fragmentation and caspase activation, resembling the progression of apoptosis. Moreover, rokitamycin reduced the mitochondrial transmembrane potential and released cytochrome c from mitochondria to the cytosol, suggesting that mitochondrial perturbation is involved in rokitamycin-induced apoptosis. These results suggest that rokitamycin possesses not only bactericidal activity but also pro-apoptotic activity in human leukemia cells.
Insights
This study reveals that rokitamycin, a macrolide antibiotic, induces programmed cell death (apoptosis) in human leukemia cells. This finding suggests potential new therapeutic applications for macrolides beyond their antibacterial effects.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Macrolides are known antibiotics with antibacterial and immunomodulating activities.
- Emerging research suggests novel physiological roles for macrolides.
Purpose of the Study:
- To investigate the potential of various macrolides to induce apoptosis in human leukemia cell lines.
- To identify specific macrolides with pro-apoptotic effects on leukemia cells.
Main Methods:
- Screening of 13 different macrolides for their effects on Jurkat and HL-60 leukemia cell viability.
- Analysis of DNA fragmentation, caspase activation, and mitochondrial membrane potential.
- Assessment of cytochrome c release from mitochondria.
Main Results:
- Rokitamycin, a 16-member ring macrolide, demonstrated significant induction of cell death in leukemia cells.
- Rokitamycin treatment led to DNA fragmentation and caspase activation, characteristic of apoptosis.
- Mitochondrial disruption, including loss of transmembrane potential and cytochrome c release, was observed.
Conclusions:
- Rokitamycin exhibits pro-apoptotic activity against human leukemia cells.
- The mechanism of rokitamycin-induced apoptosis involves mitochondrial pathways.
- These findings suggest rokitamycin as a potential agent for leukemia therapy, complementing its antibiotic functions.
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