Saporin-S6: A Useful Tool in Cancer Therapy

Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of...

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Main Authors: Letizia Polito, Massimo Bortolotti, Daniele Mercatelli, Maria Giulia Battelli, Andrea Bolognesi
Format: Article
Language:English
Published: MDPI AG 2013-10-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/5/10/1698
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author Letizia Polito
Massimo Bortolotti
Daniele Mercatelli
Maria Giulia Battelli
Andrea Bolognesi
author_facet Letizia Polito
Massimo Bortolotti
Daniele Mercatelli
Maria Giulia Battelli
Andrea Bolognesi
author_sort Letizia Polito
collection DOAJ
description Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.
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spelling doaj.art-5f253a6cdddd4b479a511f2b03b016082022-12-22T04:20:03ZengMDPI AGToxins2072-66512013-10-015101698172210.3390/toxins5101698Saporin-S6: A Useful Tool in Cancer TherapyLetizia PolitoMassimo BortolottiDaniele MercatelliMaria Giulia BattelliAndrea BolognesiThirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.http://www.mdpi.com/2072-6651/5/10/1698saporin-S6saporinSaponaria officinalisimmunotoxinimmunotherapyribosome-inactivating proteinsmonoclonal antibodiesrRNA N-glycosylase activityanti-cancer therapyhematological tumors
spellingShingle Letizia Polito
Massimo Bortolotti
Daniele Mercatelli
Maria Giulia Battelli
Andrea Bolognesi
Saporin-S6: A Useful Tool in Cancer Therapy
Toxins
saporin-S6
saporin
Saponaria officinalis
immunotoxin
immunotherapy
ribosome-inactivating proteins
monoclonal antibodies
rRNA N-glycosylase activity
anti-cancer therapy
hematological tumors
title Saporin-S6: A Useful Tool in Cancer Therapy
title_full Saporin-S6: A Useful Tool in Cancer Therapy
title_fullStr Saporin-S6: A Useful Tool in Cancer Therapy
title_full_unstemmed Saporin-S6: A Useful Tool in Cancer Therapy
title_short Saporin-S6: A Useful Tool in Cancer Therapy
title_sort saporin s6 a useful tool in cancer therapy
topic saporin-S6
saporin
Saponaria officinalis
immunotoxin
immunotherapy
ribosome-inactivating proteins
monoclonal antibodies
rRNA N-glycosylase activity
anti-cancer therapy
hematological tumors
url http://www.mdpi.com/2072-6651/5/10/1698
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AT mariagiuliabattelli saporins6ausefultoolincancertherapy
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