Ethyl acetate extract of Caesalpinia sappan L. inhibited acute myeloid leukemia via ROS-mediated apoptosis and differentiation.
Identifieur interne : 000154 ( Main/Exploration ); précédent : 000153; suivant : 000155Ethyl acetate extract of Caesalpinia sappan L. inhibited acute myeloid leukemia via ROS-mediated apoptosis and differentiation.
Auteurs : Hao-Yue Ma [République populaire de Chine] ; Cheng-Qiang Wang [République populaire de Chine] ; Hui He [République populaire de Chine] ; Zan-Yang Yu [République populaire de Chine] ; Yao Tong [République populaire de Chine] ; Gen Liu [République populaire de Chine] ; Yu-Qi Yang [République populaire de Chine] ; Li Li [République populaire de Chine] ; Lei Pang [République populaire de Chine] ; Hong-Yi Qi [République populaire de Chine]Source :
- Phytomedicine : international journal of phytotherapy and phytopharmacology [ 1618-095X ] ; 2020.
Descripteurs français
- KwdFr :
- Acétates (composition chimique), Animaux (MeSH), Antigènes CD11b (métabolisme), Antigènes CD14 (métabolisme), Antinéoplasiques d'origine végétale (composition chimique), Antinéoplasiques d'origine végétale (pharmacologie), Apoptose (effets des médicaments et des substances chimiques), Caesalpinia (composition chimique), Cellules HL-60 (MeSH), Différenciation cellulaire (effets des médicaments et des substances chimiques), Espèces réactives de l'oxygène (métabolisme), Extraits de plantes (pharmacologie), Humains (MeSH), Leucémie aigüe myéloïde (anatomopathologie), Leucémie aigüe myéloïde (métabolisme), Leucémie aigüe myéloïde (traitement médicamenteux), Potentiel de membrane mitochondriale (effets des médicaments et des substances chimiques), Souris SCID (MeSH), Souris de lignée NOD (MeSH), Tests d'activité antitumorale sur modèle de xénogreffe (MeSH).
- MESH :
- anatomopathologie : Leucémie aigüe myéloïde.
- composition chimique : Acétates, Antinéoplasiques d'origine végétale, Caesalpinia.
- effets des médicaments et des substances chimiques : Apoptose, Différenciation cellulaire, Potentiel de membrane mitochondriale.
- métabolisme : Antigènes CD11b, Antigènes CD14, Espèces réactives de l'oxygène, Leucémie aigüe myéloïde.
- pharmacologie : Antinéoplasiques d'origine végétale, Extraits de plantes.
- traitement médicamenteux : Leucémie aigüe myéloïde.
- Animaux, Cellules HL-60, Humains, Souris SCID, Souris de lignée NOD, Tests d'activité antitumorale sur modèle de xénogreffe.
English descriptors
- KwdEn :
- Acetates (chemistry), Animals (MeSH), Antineoplastic Agents, Phytogenic (chemistry), Antineoplastic Agents, Phytogenic (pharmacology), Apoptosis (drug effects), CD11b Antigen (metabolism), Caesalpinia (chemistry), Cell Differentiation (drug effects), HL-60 Cells (MeSH), Humans (MeSH), Leukemia, Myeloid, Acute (drug therapy), Leukemia, Myeloid, Acute (metabolism), Leukemia, Myeloid, Acute (pathology), Lipopolysaccharide Receptors (metabolism), Membrane Potential, Mitochondrial (drug effects), Mice, Inbred NOD (MeSH), Mice, SCID (MeSH), Plant Extracts (pharmacology), Reactive Oxygen Species (metabolism), Xenograft Model Antitumor Assays (MeSH).
- MESH :
- chemical , chemistry : Acetates, Antineoplastic Agents, Phytogenic.
- chemical , metabolism : CD11b Antigen, Lipopolysaccharide Receptors, Reactive Oxygen Species.
- chemical , pharmacology : Antineoplastic Agents, Phytogenic, Plant Extracts.
- chemistry : Caesalpinia.
- drug effects : Apoptosis, Cell Differentiation, Membrane Potential, Mitochondrial.
- drug therapy : Leukemia, Myeloid, Acute.
- metabolism : Leukemia, Myeloid, Acute.
- pathology : Leukemia, Myeloid, Acute.
- Animals, HL-60 Cells, Humans, Mice, Inbred NOD, Mice, SCID, Xenograft Model Antitumor Assays.
Abstract
BACKGROUND
The dried heartwood of Caesalpinia sappan L. is traditionally prescribed in the formula of traditional Chinese medicine (TCM) for the treatment of acute myeloid leukemia (AML), while nothing is yet known of the active fractions and the underlying mechanisms.
PURPOSE
This study aims to investigate the effect of the ethyl acetate extract of the dried heartwood of Caesalpinia sappan L. (C-A-E) on induction of apoptosis and promotion of differentiation in vitro and anti-AML activity in vivo.
STUDY DESIGN/METHODS
The aqueous extract was sequentially separated with solvents of increasing polarity and the active fraction was determined through the inhibition potency. The inhibition of the active fraction on cell viability, proliferation and colony formation was performed in different AML cells. Induction of apoptosis and the promotion of differentiation were further determined. Then, the level of the reactive oxygen species (ROS) and its potential role were assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice.
RESULTS
C-A-E exhibited the highest inhibition on the cell viability of HL-60 cells. Meanwhile, C-A-E significantly suppressed the proliferation and the colony formation ability of HL-60 and Kasumi-1 cells. Moreover, C-A-E significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. C-A-E also reduced the level of mitochondrial membrane potential, promoted the release of cytochrome C, decreased the Bcl-2/Bax ratio, and promoted the cleavage of caspase-9 and -3. In addition, Mdivi-1 (mitochondrial fission blocker) remarkably reduced the apoptosis caused by C-A-E. Meanwhile, C-A-E also induced the expression of Mff and Fis1 and increased the location of Drp1 in mitochondria. Furthermore, C-A-E obviously promoted the differentiation of AML cells characterized by the typic morphological changes, the increased NBT positive cells, as well as the increased CD11b and CD14 levels. Notably, C-A-E significantly enhanced the intracellular ROS level. Moreimportantly, C-A-E-mediated apoptosis and differentiation of HL-60 cells was significantly mitigated by NAC. Additionally, C-A-E also exhibited an obvious anti-AML effect in NOD/SCID mice with the injection of HL-60 cells.
CONCLUSIONS
C-A-E exhibited an inhibitory effect on AML cells by inducing mitochondrial apoptosis and promoting differentiation, both of which were highly correlated to the activation of ROS.
DOI: 10.1016/j.phymed.2019.153142
PubMed: 32045840
Affiliations:
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uniqKey="Yu Z" first="Zan-Yang" last="Yu">Zan-Yang Yu</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Tong, Yao" sort="Tong, Yao" uniqKey="Tong Y" first="Yao" last="Tong">Yao Tong</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 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2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Qi, Hong Yi" sort="Qi, Hong Yi" uniqKey="Qi H" first="Hong-Yi" last="Qi">Hong-Yi Qi</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China. Electronic address: hongyiqi@swu.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32045840</idno><idno type="pmid">32045840</idno><idno type="doi">10.1016/j.phymed.2019.153142</idno><idno type="wicri:Area/Main/Corpus">000217</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000217</idno><idno type="wicri:Area/Main/Curation">000217</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000217</idno><idno type="wicri:Area/Main/Exploration">000217</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Ethyl acetate extract of Caesalpinia sappan L. inhibited acute myeloid leukemia via ROS-mediated apoptosis and differentiation.</title><author><name sortKey="Ma, Hao Yue" sort="Ma, Hao Yue" uniqKey="Ma H" first="Hao-Yue" last="Ma">Hao-Yue Ma</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Cheng Qiang" sort="Wang, Cheng Qiang" uniqKey="Wang C" first="Cheng-Qiang" last="Wang">Cheng-Qiang Wang</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="He, Hui" sort="He, Hui" uniqKey="He H" first="Hui" last="He">Hui He</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Zan Yang" sort="Yu, Zan Yang" uniqKey="Yu Z" first="Zan-Yang" last="Yu">Zan-Yang Yu</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Tong, Yao" sort="Tong, Yao" uniqKey="Tong Y" first="Yao" last="Tong">Yao Tong</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Gen" sort="Liu, Gen" uniqKey="Liu G" first="Gen" last="Liu">Gen Liu</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Yu Qi" sort="Yang, Yu Qi" uniqKey="Yang Y" first="Yu-Qi" last="Yang">Yu-Qi Yang</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Pang, Lei" sort="Pang, Lei" uniqKey="Pang L" first="Lei" last="Pang">Lei Pang</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author><author><name sortKey="Qi, Hong Yi" sort="Qi, Hong Yi" uniqKey="Qi H" first="Hong-Yi" last="Qi">Hong-Yi Qi</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China. Electronic address: hongyiqi@swu.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716</wicri:regionArea><wicri:noRegion>Chongqing 400716</wicri:noRegion></affiliation></author></analytic><series><title level="j">Phytomedicine : international journal of phytotherapy and phytopharmacology</title><idno type="eISSN">1618-095X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetates (chemistry)</term><term>Animals (MeSH)</term><term>Antineoplastic Agents, Phytogenic (chemistry)</term><term>Antineoplastic Agents, Phytogenic (pharmacology)</term><term>Apoptosis (drug effects)</term><term>CD11b Antigen (metabolism)</term><term>Caesalpinia (chemistry)</term><term>Cell Differentiation (drug effects)</term><term>HL-60 Cells (MeSH)</term><term>Humans (MeSH)</term><term>Leukemia, Myeloid, Acute (drug therapy)</term><term>Leukemia, Myeloid, Acute (metabolism)</term><term>Leukemia, Myeloid, Acute (pathology)</term><term>Lipopolysaccharide Receptors (metabolism)</term><term>Membrane Potential, Mitochondrial (drug effects)</term><term>Mice, Inbred NOD (MeSH)</term><term>Mice, SCID (MeSH)</term><term>Plant Extracts (pharmacology)</term><term>Reactive Oxygen Species (metabolism)</term><term>Xenograft Model Antitumor Assays (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acétates (composition chimique)</term><term>Animaux (MeSH)</term><term>Antigènes CD11b (métabolisme)</term><term>Antigènes CD14 (métabolisme)</term><term>Antinéoplasiques d'origine végétale (composition chimique)</term><term>Antinéoplasiques d'origine végétale (pharmacologie)</term><term>Apoptose (effets des médicaments et des substances chimiques)</term><term>Caesalpinia (composition chimique)</term><term>Cellules HL-60 (MeSH)</term><term>Différenciation cellulaire (effets des médicaments et des substances chimiques)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Extraits de plantes (pharmacologie)</term><term>Humains (MeSH)</term><term>Leucémie aigüe myéloïde (anatomopathologie)</term><term>Leucémie aigüe myéloïde (métabolisme)</term><term>Leucémie aigüe myéloïde (traitement médicamenteux)</term><term>Potentiel de membrane mitochondriale (effets des médicaments et des substances chimiques)</term><term>Souris SCID (MeSH)</term><term>Souris de lignée NOD (MeSH)</term><term>Tests d'activité antitumorale sur modèle de xénogreffe (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Acetates</term><term>Antineoplastic Agents, Phytogenic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>CD11b Antigen</term><term>Lipopolysaccharide Receptors</term><term>Reactive Oxygen Species</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents, Phytogenic</term><term>Plant Extracts</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Leucémie aigüe myéloïde</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Caesalpinia</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Acétates</term><term>Antinéoplasiques d'origine végétale</term><term>Caesalpinia</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Cell Differentiation</term><term>Membrane Potential, Mitochondrial</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Myeloid, Acute</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term><term>Différenciation cellulaire</term><term>Potentiel de membrane mitochondriale</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Leukemia, Myeloid, Acute</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes CD11b</term><term>Antigènes CD14</term><term>Espèces réactives de l'oxygène</term><term>Leucémie aigüe myéloïde</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Leukemia, Myeloid, Acute</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques d'origine végétale</term><term>Extraits de plantes</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie aigüe myéloïde</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>HL-60 Cells</term><term>Humans</term><term>Mice, Inbred NOD</term><term>Mice, SCID</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HL-60</term><term>Humains</term><term>Souris SCID</term><term>Souris de lignée NOD</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>The dried heartwood of Caesalpinia sappan L. is traditionally prescribed in the formula of traditional Chinese medicine (TCM) for the treatment of acute myeloid leukemia (AML), while nothing is yet known of the active fractions and the underlying mechanisms.</p></div><div type="abstract" xml:lang="en"><p><b>PURPOSE</b></p><p>This study aims to investigate the effect of the ethyl acetate extract of the dried heartwood of Caesalpinia sappan L. (C-A-E) on induction of apoptosis and promotion of differentiation in vitro and anti-AML activity in vivo.</p></div><div type="abstract" xml:lang="en"><p><b>STUDY DESIGN/METHODS</b></p><p>The aqueous extract was sequentially separated with solvents of increasing polarity and the active fraction was determined through the inhibition potency. The inhibition of the active fraction on cell viability, proliferation and colony formation was performed in different AML cells. Induction of apoptosis and the promotion of differentiation were further determined. Then, the level of the reactive oxygen species (ROS) and its potential role were assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>C-A-E exhibited the highest inhibition on the cell viability of HL-60 cells. Meanwhile, C-A-E significantly suppressed the proliferation and the colony formation ability of HL-60 and Kasumi-1 cells. Moreover, C-A-E significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. C-A-E also reduced the level of mitochondrial membrane potential, promoted the release of cytochrome C, decreased the Bcl-2/Bax ratio, and promoted the cleavage of caspase-9 and -3. In addition, Mdivi-1 (mitochondrial fission blocker) remarkably reduced the apoptosis caused by C-A-E. Meanwhile, C-A-E also induced the expression of Mff and Fis1 and increased the location of Drp1 in mitochondria. Furthermore, C-A-E obviously promoted the differentiation of AML cells characterized by the typic morphological changes, the increased NBT positive cells, as well as the increased CD11b and CD14 levels. Notably, C-A-E significantly enhanced the intracellular ROS level. Moreimportantly, C-A-E-mediated apoptosis and differentiation of HL-60 cells was significantly mitigated by NAC. Additionally, C-A-E also exhibited an obvious anti-AML effect in NOD/SCID mice with the injection of HL-60 cells.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>C-A-E exhibited an inhibitory effect on AML cells by inducing mitochondrial apoptosis and promoting differentiation, both of which were highly correlated to the activation of ROS.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Curated" Owner="NLM"><PMID Version="1">32045840</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>11</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1618-095X</ISSN><JournalIssue CitedMedium="Internet"><Volume>68</Volume><PubDate><Year>2020</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Phytomedicine : international journal of phytotherapy and phytopharmacology</Title><ISOAbbreviation>Phytomedicine</ISOAbbreviation></Journal><ArticleTitle>Ethyl acetate extract of Caesalpinia sappan L. inhibited acute myeloid leukemia via ROS-mediated apoptosis and differentiation.</ArticleTitle><Pagination><MedlinePgn>153142</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0944-7113(19)30458-1</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.phymed.2019.153142</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The dried heartwood of Caesalpinia sappan L. is traditionally prescribed in the formula of traditional Chinese medicine (TCM) for the treatment of acute myeloid leukemia (AML), while nothing is yet known of the active fractions and the underlying mechanisms.</AbstractText><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">This study aims to investigate the effect of the ethyl acetate extract of the dried heartwood of Caesalpinia sappan L. (C-A-E) on induction of apoptosis and promotion of differentiation in vitro and anti-AML activity in vivo.</AbstractText><AbstractText Label="STUDY DESIGN/METHODS" NlmCategory="METHODS">The aqueous extract was sequentially separated with solvents of increasing polarity and the active fraction was determined through the inhibition potency. The inhibition of the active fraction on cell viability, proliferation and colony formation was performed in different AML cells. Induction of apoptosis and the promotion of differentiation were further determined. Then, the level of the reactive oxygen species (ROS) and its potential role were assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">C-A-E exhibited the highest inhibition on the cell viability of HL-60 cells. Meanwhile, C-A-E significantly suppressed the proliferation and the colony formation ability of HL-60 and Kasumi-1 cells. Moreover, C-A-E significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. C-A-E also reduced the level of mitochondrial membrane potential, promoted the release of cytochrome C, decreased the Bcl-2/Bax ratio, and promoted the cleavage of caspase-9 and -3. In addition, Mdivi-1 (mitochondrial fission blocker) remarkably reduced the apoptosis caused by C-A-E. Meanwhile, C-A-E also induced the expression of Mff and Fis1 and increased the location of Drp1 in mitochondria. Furthermore, C-A-E obviously promoted the differentiation of AML cells characterized by the typic morphological changes, the increased NBT positive cells, as well as the increased CD11b and CD14 levels. Notably, C-A-E significantly enhanced the intracellular ROS level. Moreimportantly, C-A-E-mediated apoptosis and differentiation of HL-60 cells was significantly mitigated by NAC. Additionally, C-A-E also exhibited an obvious anti-AML effect in NOD/SCID mice with the injection of HL-60 cells.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">C-A-E exhibited an inhibitory effect on AML cells by inducing mitochondrial apoptosis and promoting differentiation, both of which were highly correlated to the activation of ROS.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier GmbH. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Hao-Yue</ForeName><Initials>HY</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Cheng-Qiang</ForeName><Initials>CQ</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Hui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Zan-Yang</ForeName><Initials>ZY</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tong</LastName><ForeName>Yao</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Gen</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Yu-Qi</ForeName><Initials>YQ</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pang</LastName><ForeName>Lei</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qi</LastName><ForeName>Hong-Yi</ForeName><Initials>HY</Initials><AffiliationInfo><Affiliation>College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400716, China. Electronic address: hongyiqi@swu.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>12</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Phytomedicine</MedlineTA><NlmUniqueID>9438794</NlmUniqueID><ISSNLinking>0944-7113</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000085">Acetates</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000972">Antineoplastic Agents, Phytogenic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039481">CD11b Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000632510">CD14 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C509295">ITGAM protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018950">Lipopolysaccharide Receptors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010936">Plant Extracts</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017382">Reactive Oxygen Species</NameOfSubstance></Chemical><Chemical><RegistryNumber>76845O8NMZ</RegistryNumber><NameOfSubstance UI="C007650">ethyl acetate</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000085" MajorTopicYN="N">Acetates</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000972" MajorTopicYN="N">Antineoplastic Agents, Phytogenic</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D039481" MajorTopicYN="N">CD11b Antigen</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D029911" MajorTopicYN="N">Caesalpinia</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018922" MajorTopicYN="N">HL-60 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015470" MajorTopicYN="N">Leukemia, Myeloid, Acute</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018950" MajorTopicYN="N">Lipopolysaccharide Receptors</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053078" MajorTopicYN="N">Membrane Potential, Mitochondrial</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016688" MajorTopicYN="N">Mice, Inbred NOD</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016513" MajorTopicYN="N">Mice, SCID</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010936" MajorTopicYN="N">Plant Extracts</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017382" MajorTopicYN="N">Reactive Oxygen Species</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Acute myeloid leukemia</Keyword><Keyword MajorTopicYN="N">Apoptosis</Keyword><Keyword MajorTopicYN="N">Caesalpinia sappan L.</Keyword><Keyword MajorTopicYN="N">Differentiation</Keyword><Keyword MajorTopicYN="N">Reactive oxygen species</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare that there are no conflicts of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>06</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>12</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>12</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32045840</ArticleId><ArticleId IdType="pii">S0944-7113(19)30458-1</ArticleId><ArticleId IdType="doi">10.1016/j.phymed.2019.153142</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Ma, Hao Yue" sort="Ma, Hao Yue" uniqKey="Ma H" first="Hao-Yue" last="Ma">Hao-Yue Ma</name></noRegion><name sortKey="He, Hui" sort="He, Hui" uniqKey="He H" first="Hui" last="He">Hui He</name><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name><name sortKey="Liu, Gen" sort="Liu, Gen" uniqKey="Liu G" first="Gen" last="Liu">Gen Liu</name><name sortKey="Pang, Lei" sort="Pang, Lei" uniqKey="Pang L" first="Lei" last="Pang">Lei Pang</name><name sortKey="Qi, Hong Yi" sort="Qi, Hong Yi" uniqKey="Qi H" first="Hong-Yi" last="Qi">Hong-Yi Qi</name><name sortKey="Tong, Yao" sort="Tong, Yao" uniqKey="Tong Y" first="Yao" last="Tong">Yao Tong</name><name sortKey="Wang, Cheng Qiang" sort="Wang, Cheng Qiang" uniqKey="Wang C" first="Cheng-Qiang" last="Wang">Cheng-Qiang Wang</name><name sortKey="Yang, Yu Qi" sort="Yang, Yu Qi" uniqKey="Yang Y" first="Yu-Qi" last="Yang">Yu-Qi Yang</name><name sortKey="Yu, Zan Yang" sort="Yu, Zan Yang" uniqKey="Yu Z" first="Zan-Yang" last="Yu">Zan-Yang Yu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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