Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling
Stenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Adenia stenodactyla Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactiv...
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doaj-35680d1231d54f88bbc6604c63d3a7bb2020-11-25T03:16:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00630540886Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic SignalingDaniele Mercatelli0Daniele Mercatelli1Massimo Bortolotti2Vibeke Andresen3Vibeke Andresen4André Sulen5Letizia Polito6Bjørn Tore Gjertsen7Bjørn Tore Gjertsen8Andrea Bolognesi9Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology-FaBiT, Alma Mater Studiorum, University of Bologna, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Bologna, ItalyCentre of Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, NorwayHematology Section, Department of Internal Medicine, Haukeland University Hospital, Bergen, NorwayCentre of Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Bologna, ItalyCentre of Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, NorwayHematology Section, Department of Internal Medicine, Haukeland University Hospital, Bergen, NorwayDepartment of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Bologna, ItalyStenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Adenia stenodactyla Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactive oxygen species. We analyzed the effect of stenodactylin on Raji and Ramos (Human Burkitt’s lymphoma cells) and MOLM-13 (acute myeloid leukemia cells). Moreover, we focused on the early events in MOLM-13 cells that characterize the cellular response to the toxin by whole-genome microarray analysis of gene expression. Treatment with stenodactylin induced the depurination of 28S rRNA within 4 h and increased the phosphorylation of p38 and JNK. A time-dependent activation of caspase 1, 2, 8, 9, 3/7 was also observed. Genome-wide gene expression microarray analysis revealed early changes in the expression of genes involved in the regulation of cell death, inflammation and stress response. After 4 h, a significant increase of transcript level was detectable for ATF3, BTG2, DUSP1, EGR1, and JUN. Increased upstream JUN signaling was also confirmed at protein level. The early response to stenodactylin treatment involves inflammatory and apoptotic signaling compatible with the activation of multiple cell death pathways. Because of the above described properties toward acute myeloid leukemia cells, stenodactylin may be a promising candidate for the design of new immunoconjugates for experimental cancer treatment.https://www.frontiersin.org/article/10.3389/fphar.2020.00630/fullacute myeloid leukemiaapoptosisplant toxinsribosome-inactivating proteinstenodactylintoxic lectins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniele Mercatelli Daniele Mercatelli Massimo Bortolotti Vibeke Andresen Vibeke Andresen André Sulen Letizia Polito Bjørn Tore Gjertsen Bjørn Tore Gjertsen Andrea Bolognesi |
spellingShingle |
Daniele Mercatelli Daniele Mercatelli Massimo Bortolotti Vibeke Andresen Vibeke Andresen André Sulen Letizia Polito Bjørn Tore Gjertsen Bjørn Tore Gjertsen Andrea Bolognesi Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling Frontiers in Pharmacology acute myeloid leukemia apoptosis plant toxins ribosome-inactivating protein stenodactylin toxic lectins |
author_facet |
Daniele Mercatelli Daniele Mercatelli Massimo Bortolotti Vibeke Andresen Vibeke Andresen André Sulen Letizia Polito Bjørn Tore Gjertsen Bjørn Tore Gjertsen Andrea Bolognesi |
author_sort |
Daniele Mercatelli |
title |
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling |
title_short |
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling |
title_full |
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling |
title_fullStr |
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling |
title_full_unstemmed |
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling |
title_sort |
early response to the plant toxin stenodactylin in acute myeloid leukemia cells involves inflammatory and apoptotic signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-05-01 |
description |
Stenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Adenia stenodactyla Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactive oxygen species. We analyzed the effect of stenodactylin on Raji and Ramos (Human Burkitt’s lymphoma cells) and MOLM-13 (acute myeloid leukemia cells). Moreover, we focused on the early events in MOLM-13 cells that characterize the cellular response to the toxin by whole-genome microarray analysis of gene expression. Treatment with stenodactylin induced the depurination of 28S rRNA within 4 h and increased the phosphorylation of p38 and JNK. A time-dependent activation of caspase 1, 2, 8, 9, 3/7 was also observed. Genome-wide gene expression microarray analysis revealed early changes in the expression of genes involved in the regulation of cell death, inflammation and stress response. After 4 h, a significant increase of transcript level was detectable for ATF3, BTG2, DUSP1, EGR1, and JUN. Increased upstream JUN signaling was also confirmed at protein level. The early response to stenodactylin treatment involves inflammatory and apoptotic signaling compatible with the activation of multiple cell death pathways. Because of the above described properties toward acute myeloid leukemia cells, stenodactylin may be a promising candidate for the design of new immunoconjugates for experimental cancer treatment. |
topic |
acute myeloid leukemia apoptosis plant toxins ribosome-inactivating protein stenodactylin toxic lectins |
url |
https://www.frontiersin.org/article/10.3389/fphar.2020.00630/full |
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