A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells
Rohitukine, a chromone alkaloid extracted from Dysoxylum binectariferum, has a propitious anticancer activity. Our previous study shows that a new Rohitukine derivative IIIM‐290 restricts the growth of pancreatic cancer in vivo and in vitro. In the present findings, we report the mechanism of cell d...
Gespeichert in:
| Veröffentlicht in: | Molecular carcinogenesis 2021-10, Vol.60 (10), p.671-683 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 683 |
|---|---|
| container_issue | 10 |
| container_start_page | 671 |
| container_title | Molecular carcinogenesis |
| container_volume | 60 |
| creator | Mintoo, Mubashir Khan, Sameer Wani, Abubakar Malik, Sumera Bhurta, Deendyal Bharate, Sandip Malik, Fayaz Mondhe, Dilip |
| description | Rohitukine, a chromone alkaloid extracted from Dysoxylum binectariferum, has a propitious anticancer activity. Our previous study shows that a new Rohitukine derivative IIIM‐290 restricts the growth of pancreatic cancer in vivo and in vitro. In the present findings, we report the mechanism of cell death induced by IIIM‐290 in MOLT‐4 cells (acute lymphoblastic leukemia) and its anticancer potential against various murine leukemic tumor models in vivo. We found that IIIM‐290 induced apoptosis through upregulation of different apoptotic proteins like PUMA, BAX, cytochrome c, cleaved (active) caspase‐3, and cleaved PARP in MOLT‐4 cells. Moreover, IIIM‐290 abated mitochondrial membrane potential, elevated calcium levels, reactive oxygen species, and arrested growth of MOLT‐4 cells in the synthesis (S) phase of the cell cycle. Interestingly, the elevation in proapoptotic markers was p53 dependent—the silencing of p53 abrogated apoptosis (programmed cell death) triggered by IIIM‐290 in MOLT‐4 cells. Furthermore, IIIM‐290 significantly enhanced the survival of animals with P388 and L1210 leukemia. Thus, our results put IIIM‐290 as a potential candidate for the anticancer lead. |
| doi_str_mv | 10.1002/mc.23332 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2557228801</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2571879339</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3262-dbf1b11ada4782e09bdfaf9cd1c65d378ff0fdff13d9ef0652b9b1a8c8ba1faf3</originalsourceid><addsrcrecordid>eNp10d1KwzAcBfAgCs4p-AgBb7zpzMe6Jpdj-FGYeKPXJU3-YdnapibtZHc-gs_ok9g5QRC8Ojc_DgcOQpeUTCgh7KbWE8Y5Z0doRIkUCcum02M0IkLKhEqRnaKzGNeEUJqlZIS2cxz8ynX9xjWADQS3VZ3bAs7z_PHz_YNJgl1jeg0RtykfRAuNgabDteu8XvnGBKcqrFrfdj66OGisdN8BrnZ1u_JlpWLnNK6g30DtFNZQVfEcnVhVRbj4yTF6ubt9Xjwky6f7fDFfJpqzGUtMaWlJqTJqmgkGRJbGKiu1oXqWGp4Ja4k11lJuJFgyS1kpS6qEFqWig-RjdH3obYN_7SF2Re3ifoFqwPexYGmaMSYEoQO9-kPXvg_NsG5QGRWZ5Fz-FurgYwxgiza4WoVdQUmxP6CodfF9wECTA31zFez-dcXj4uC_AJMDiTc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2571879339</pqid></control><display><type>article</type><title>A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells</title><source>Wiley Online Library - AutoHoldings Journals</source><creator>Mintoo, Mubashir ; Khan, Sameer ; Wani, Abubakar ; Malik, Sumera ; Bhurta, Deendyal ; Bharate, Sandip ; Malik, Fayaz ; Mondhe, Dilip</creator><creatorcontrib>Mintoo, Mubashir ; Khan, Sameer ; Wani, Abubakar ; Malik, Sumera ; Bhurta, Deendyal ; Bharate, Sandip ; Malik, Fayaz ; Mondhe, Dilip</creatorcontrib><description>Rohitukine, a chromone alkaloid extracted from Dysoxylum binectariferum, has a propitious anticancer activity. Our previous study shows that a new Rohitukine derivative IIIM‐290 restricts the growth of pancreatic cancer in vivo and in vitro. In the present findings, we report the mechanism of cell death induced by IIIM‐290 in MOLT‐4 cells (acute lymphoblastic leukemia) and its anticancer potential against various murine leukemic tumor models in vivo. We found that IIIM‐290 induced apoptosis through upregulation of different apoptotic proteins like PUMA, BAX, cytochrome c, cleaved (active) caspase‐3, and cleaved PARP in MOLT‐4 cells. Moreover, IIIM‐290 abated mitochondrial membrane potential, elevated calcium levels, reactive oxygen species, and arrested growth of MOLT‐4 cells in the synthesis (S) phase of the cell cycle. Interestingly, the elevation in proapoptotic markers was p53 dependent—the silencing of p53 abrogated apoptosis (programmed cell death) triggered by IIIM‐290 in MOLT‐4 cells. Furthermore, IIIM‐290 significantly enhanced the survival of animals with P388 and L1210 leukemia. Thus, our results put IIIM‐290 as a potential candidate for the anticancer lead.</description><identifier>ISSN: 0899-1987</identifier><identifier>EISSN: 1098-2744</identifier><identifier>DOI: 10.1002/mc.23332</identifier><language>eng</language><publisher>Austin: Wiley Subscription Services, Inc</publisher><subject>Acute lymphoblastic leukemia ; Animal models ; Antitumor activity ; Apoptosis ; BAX protein ; Calcium (mitochondrial) ; Cancer ; Caspase ; CDK‐9 ; Cell cycle ; Cell death ; Cytochrome c ; L1210 ; Leukemia ; Lymphatic leukemia ; Membrane potential ; Mitochondria ; Molting ; MOLT‐4 ; P388 ; p53 Protein ; Pancreatic cancer ; Reactive oxygen species</subject><ispartof>Molecular carcinogenesis, 2021-10, Vol.60 (10), p.671-683</ispartof><rights>2021 Wiley Periodicals LLC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3262-dbf1b11ada4782e09bdfaf9cd1c65d378ff0fdff13d9ef0652b9b1a8c8ba1faf3</citedby><cites>FETCH-LOGICAL-c3262-dbf1b11ada4782e09bdfaf9cd1c65d378ff0fdff13d9ef0652b9b1a8c8ba1faf3</cites><orcidid>0000-0002-3024-2647</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmc.23332$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmc.23332$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Mintoo, Mubashir</creatorcontrib><creatorcontrib>Khan, Sameer</creatorcontrib><creatorcontrib>Wani, Abubakar</creatorcontrib><creatorcontrib>Malik, Sumera</creatorcontrib><creatorcontrib>Bhurta, Deendyal</creatorcontrib><creatorcontrib>Bharate, Sandip</creatorcontrib><creatorcontrib>Malik, Fayaz</creatorcontrib><creatorcontrib>Mondhe, Dilip</creatorcontrib><title>A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells</title><title>Molecular carcinogenesis</title><description>Rohitukine, a chromone alkaloid extracted from Dysoxylum binectariferum, has a propitious anticancer activity. Our previous study shows that a new Rohitukine derivative IIIM‐290 restricts the growth of pancreatic cancer in vivo and in vitro. In the present findings, we report the mechanism of cell death induced by IIIM‐290 in MOLT‐4 cells (acute lymphoblastic leukemia) and its anticancer potential against various murine leukemic tumor models in vivo. We found that IIIM‐290 induced apoptosis through upregulation of different apoptotic proteins like PUMA, BAX, cytochrome c, cleaved (active) caspase‐3, and cleaved PARP in MOLT‐4 cells. Moreover, IIIM‐290 abated mitochondrial membrane potential, elevated calcium levels, reactive oxygen species, and arrested growth of MOLT‐4 cells in the synthesis (S) phase of the cell cycle. Interestingly, the elevation in proapoptotic markers was p53 dependent—the silencing of p53 abrogated apoptosis (programmed cell death) triggered by IIIM‐290 in MOLT‐4 cells. Furthermore, IIIM‐290 significantly enhanced the survival of animals with P388 and L1210 leukemia. Thus, our results put IIIM‐290 as a potential candidate for the anticancer lead.</description><subject>Acute lymphoblastic leukemia</subject><subject>Animal models</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>BAX protein</subject><subject>Calcium (mitochondrial)</subject><subject>Cancer</subject><subject>Caspase</subject><subject>CDK‐9</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cytochrome c</subject><subject>L1210</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Membrane potential</subject><subject>Mitochondria</subject><subject>Molting</subject><subject>MOLT‐4</subject><subject>P388</subject><subject>p53 Protein</subject><subject>Pancreatic cancer</subject><subject>Reactive oxygen species</subject><issn>0899-1987</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10d1KwzAcBfAgCs4p-AgBb7zpzMe6Jpdj-FGYeKPXJU3-YdnapibtZHc-gs_ok9g5QRC8Ojc_DgcOQpeUTCgh7KbWE8Y5Z0doRIkUCcum02M0IkLKhEqRnaKzGNeEUJqlZIS2cxz8ynX9xjWADQS3VZ3bAs7z_PHz_YNJgl1jeg0RtykfRAuNgabDteu8XvnGBKcqrFrfdj66OGisdN8BrnZ1u_JlpWLnNK6g30DtFNZQVfEcnVhVRbj4yTF6ubt9Xjwky6f7fDFfJpqzGUtMaWlJqTJqmgkGRJbGKiu1oXqWGp4Ja4k11lJuJFgyS1kpS6qEFqWig-RjdH3obYN_7SF2Re3ifoFqwPexYGmaMSYEoQO9-kPXvg_NsG5QGRWZ5Fz-FurgYwxgiza4WoVdQUmxP6CodfF9wECTA31zFez-dcXj4uC_AJMDiTc</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Mintoo, Mubashir</creator><creator>Khan, Sameer</creator><creator>Wani, Abubakar</creator><creator>Malik, Sumera</creator><creator>Bhurta, Deendyal</creator><creator>Bharate, Sandip</creator><creator>Malik, Fayaz</creator><creator>Mondhe, Dilip</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3024-2647</orcidid></search><sort><creationdate>202110</creationdate><title>A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells</title><author>Mintoo, Mubashir ; Khan, Sameer ; Wani, Abubakar ; Malik, Sumera ; Bhurta, Deendyal ; Bharate, Sandip ; Malik, Fayaz ; Mondhe, Dilip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3262-dbf1b11ada4782e09bdfaf9cd1c65d378ff0fdff13d9ef0652b9b1a8c8ba1faf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Animal models</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>BAX protein</topic><topic>Calcium (mitochondrial)</topic><topic>Cancer</topic><topic>Caspase</topic><topic>CDK‐9</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Cytochrome c</topic><topic>L1210</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Membrane potential</topic><topic>Mitochondria</topic><topic>Molting</topic><topic>MOLT‐4</topic><topic>P388</topic><topic>p53 Protein</topic><topic>Pancreatic cancer</topic><topic>Reactive oxygen species</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mintoo, Mubashir</creatorcontrib><creatorcontrib>Khan, Sameer</creatorcontrib><creatorcontrib>Wani, Abubakar</creatorcontrib><creatorcontrib>Malik, Sumera</creatorcontrib><creatorcontrib>Bhurta, Deendyal</creatorcontrib><creatorcontrib>Bharate, Sandip</creatorcontrib><creatorcontrib>Malik, Fayaz</creatorcontrib><creatorcontrib>Mondhe, Dilip</creatorcontrib><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular carcinogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mintoo, Mubashir</au><au>Khan, Sameer</au><au>Wani, Abubakar</au><au>Malik, Sumera</au><au>Bhurta, Deendyal</au><au>Bharate, Sandip</au><au>Malik, Fayaz</au><au>Mondhe, Dilip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells</atitle><jtitle>Molecular carcinogenesis</jtitle><date>2021-10</date><risdate>2021</risdate><volume>60</volume><issue>10</issue><spage>671</spage><epage>683</epage><pages>671-683</pages><issn>0899-1987</issn><eissn>1098-2744</eissn><abstract>Rohitukine, a chromone alkaloid extracted from Dysoxylum binectariferum, has a propitious anticancer activity. Our previous study shows that a new Rohitukine derivative IIIM‐290 restricts the growth of pancreatic cancer in vivo and in vitro. In the present findings, we report the mechanism of cell death induced by IIIM‐290 in MOLT‐4 cells (acute lymphoblastic leukemia) and its anticancer potential against various murine leukemic tumor models in vivo. We found that IIIM‐290 induced apoptosis through upregulation of different apoptotic proteins like PUMA, BAX, cytochrome c, cleaved (active) caspase‐3, and cleaved PARP in MOLT‐4 cells. Moreover, IIIM‐290 abated mitochondrial membrane potential, elevated calcium levels, reactive oxygen species, and arrested growth of MOLT‐4 cells in the synthesis (S) phase of the cell cycle. Interestingly, the elevation in proapoptotic markers was p53 dependent—the silencing of p53 abrogated apoptosis (programmed cell death) triggered by IIIM‐290 in MOLT‐4 cells. Furthermore, IIIM‐290 significantly enhanced the survival of animals with P388 and L1210 leukemia. Thus, our results put IIIM‐290 as a potential candidate for the anticancer lead.</abstract><cop>Austin</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/mc.23332</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-3024-2647</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0899-1987 |
| ispartof | Molecular carcinogenesis, 2021-10, Vol.60 (10), p.671-683 |
| issn | 0899-1987 1098-2744 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2557228801 |
| source | Wiley Online Library - AutoHoldings Journals |
| subjects | Acute lymphoblastic leukemia Animal models Antitumor activity Apoptosis BAX protein Calcium (mitochondrial) Cancer Caspase CDK‐9 Cell cycle Cell death Cytochrome c L1210 Leukemia Lymphatic leukemia Membrane potential Mitochondria Molting MOLT‐4 P388 p53 Protein Pancreatic cancer Reactive oxygen species |
| title | A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T05%3A53%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20rohitukine%20derivative%20IIIM%E2%80%90290%20induces%20p53%20dependent%20mitochondrial%20apoptosis%20in%20acute%20lymphoblastic%20leukemia%20cells&rft.jtitle=Molecular%20carcinogenesis&rft.au=Mintoo,%20Mubashir&rft.date=2021-10&rft.volume=60&rft.issue=10&rft.spage=671&rft.epage=683&rft.pages=671-683&rft.issn=0899-1987&rft.eissn=1098-2744&rft_id=info:doi/10.1002/mc.23332&rft_dat=%3Cproquest_cross%3E2571879339%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2571879339&rft_id=info:pmid/&rfr_iscdi=true |