The apoptotic effect of somatostatin analogue SMS 201-995 on human lymphocytes
D Lattuada1, C Casnici, A Venuto
1Department of Pharmacology, School of Medicine, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy
Abstract:
The antiproliferative effect of a synthetic octapeptide, somatostatin analogue SMS 201-995 (SMS), and its capacity to bind were evaluated on human peripheral blood lymphocytes (PBL) activated by phytohemoagglutinin (PHA). We then addressed our work to investigate if SMS inhibits PHA activation of PBL by a cytostatic rather than a cytotoxic mechanism. Consequently, we studied the cell cycle distribution and the activation of caspase-3, measuring the presence of the cleavage product of poly(ADP-ribose) polymerases (PARP), and we evaluated the presence of apoptotic DNA by using a monoclonal antibody specific for the single-stranded regions of DNA. All our results indicate that SMS induces apoptosis in activated lymphocytes.
Insights
The synthetic octapeptide somatostatin analogue SMS 201-995 (SMS) was found to inhibit human peripheral blood lymphocytes (PBL) activation. SMS induces apoptosis, programmed cell death, in activated lymphocytes rather than acting as a cytotoxic agent.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Phytohemoagglutinin (PHA) activates human peripheral blood lymphocytes (PBL).
- Somatostatin analogue SMS 201-995 (SMS) is a synthetic octapeptide with antiproliferative effects.
- The mechanism of SMS action on activated PBL requires elucidation, specifically whether it is cytostatic or cytotoxic.
Purpose of the Study:
- To investigate the antiproliferative effect and binding capacity of SMS on PHA-activated human PBL.
- To determine if SMS inhibits PHA-induced PBL activation via a cytostatic or cytotoxic mechanism.
- To analyze the induction of apoptosis in activated lymphocytes by SMS.
Main Methods:
- Evaluation of SMS binding and antiproliferative effects on PHA-activated PBL.
- Cell cycle distribution analysis.
- Measurement of caspase-3 activation and poly(ADP-ribose) polymerases (PARP) cleavage product.
- Detection of apoptotic DNA using a specific monoclonal antibody.
Main Results:
- SMS exhibits antiproliferative effects on PHA-activated human PBL.
- SMS induces apoptosis in activated lymphocytes.
- Evidence suggests a cytostatic rather than cytotoxic mechanism of action for SMS.
Conclusions:
- SMS 201-995 induces apoptosis in PHA-activated human peripheral blood lymphocytes.
- The findings indicate that SMS exerts its antiproliferative effects through an apoptotic pathway.
- SMS acts as a cytostatic agent by inducing programmed cell death in activated lymphocytes.
