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Induction of apoptosis in human leukemic U937 cells by tetrandrine
Abstract:
Tetrandrine, a calcium channel antagonist, is a plant alkaloid possessing various pharmacological activities including anti-tumor activity. We studied tetrandrine to determine whether or not this anti-tumor effect occurs through induction of apoptosis. Tetrandrine inhibited both proliferation and clonogenicity of human leukemic U937 cells at an optimal concentration of 2.5 microg/ml. This growth inhibition was dose and time dependent, and accompanied with evidence of apoptotic changes. The characteristic morphological changes of apoptosis were observed in U937 cells under light microscopy and DNA fragmentation was noted by gel electrophoresis. Moreover, flow cytometric detection of surface phosphatidyl serine expression of U937 cells after treatment with tetrandrine confirmed the induction of apoptosis in these cells. The induction of apoptosis by tetrandrine would appear to proceed via non-Ca2+-dependent pathways.
Insights
Tetrandrine, a plant alkaloid, effectively inhibits human leukemia cell growth by inducing apoptosis. This anti-tumor effect occurs through non-calcium-dependent pathways, offering potential therapeutic insights.
Area of Science:
- Pharmacology
- Cancer Biology
- Cell Biology
Background:
- Tetrandrine is a plant alkaloid known for its calcium channel antagonist properties.
- It exhibits various pharmacological activities, including potential anti-tumor effects.
- The precise mechanism of tetrandrine's anti-tumor activity requires further elucidation.
Purpose of the Study:
- To investigate whether the anti-tumor effect of tetrandrine is mediated by the induction of apoptosis.
- To determine the optimal concentration of tetrandrine for inhibiting human leukemic U937 cell proliferation and clonogenicity.
- To explore the pathways involved in tetrandrine-induced apoptosis.
Main Methods:
- Human leukemic U937 cells were treated with varying concentrations of tetrandrine.
- Cell proliferation and clonogenicity assays were performed.
- Morphological changes indicative of apoptosis were assessed using light microscopy.
- DNA fragmentation was analyzed via gel electrophoresis.
- Apoptosis induction was confirmed using flow cytometry to detect phosphatidylserine expression.
Main Results:
- Tetrandrine significantly inhibited U937 cell proliferation and clonogenicity in a dose- and time-dependent manner.
- The optimal inhibitory concentration was determined to be 2.5 microg/ml.
- Morphological and biochemical evidence confirmed the induction of apoptosis in treated cells.
- Flow cytometry validated the induction of apoptosis by tetrandrine.
Conclusions:
- Tetrandrine demonstrates potent anti-leukemic activity through the induction of apoptosis in U937 cells.
- The anti-tumor effect of tetrandrine appears to be mediated via non-calcium-dependent pathways.
- These findings suggest tetrandrine as a potential therapeutic agent for leukemia.