Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06
Background Acridine compounds have been described as promising anticancer agents. Previous studies showed that ( E )-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor an...
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| Veröffentlicht in: | Pharmacological reports 2022-06, Vol.74 (3), p.545-554 |
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| creator | Duarte, Sâmia Sousa Silva, Daiana Karla Frade Lisboa, Thaís Mangeon Honorato Gouveia, Rawny Galdino de Andrade, Camyla Caroliny Neves de Sousa, Valgrícia Matias Ferreira, Rafael Carlos de Moura, Ricardo Olimpio Gomes, Joilly Nilce Santana da Silva, Patricia Mirella de Lourdes Assunção Araújo de Azevedo, Fátima Keesen, Tatjana S. L. Gonçalves, Juan Carlos Ramos Batista, Leônia Maria Sobral, Marianna Vieira |
| description | Background
Acridine compounds have been described as promising anticancer agents. Previous studies showed that (
E
)-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro.
Methods
MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125–200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC
50
) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide—PI—staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test.
Results
AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC
50
: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (
p
|
| doi_str_mv | 10.1007/s43440-022-00357-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2640321688</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2640321688</sourcerecordid><originalsourceid>FETCH-LOGICAL-c347t-7817ed75cd20e34e410790a4a223c22c2bd47308afda31eaeaa9d8c1b729aa923</originalsourceid><addsrcrecordid>eNp9kEFPHCEYholpo1vtH-jBcPQg7ccHM8wcN5tWm9h4Wc-EBabBzMAIM4n-e7Fre-yBfASe9w08hHzh8JUDqG9FCimBASIDEI1icEI2iH3PmraTH8iGKyEZ5xLOyKdSHgEkR9GckjPRYK9qZkPidk7zkpZgqYmuriWk5-DqpH4YvF0KDZHe7va1p6U2jSnXQzNSa7INMU2GWj-OhR5eqKFlDjkxY3NwIfqKT3Nao7um21_77Y5Be0E-DmYs_vP7PCcPP77vd7fs7v7m5257x6yQamGq48o71ViH4IX0koPqwUiDKCyixYOTSkBnBmcE98Yb07vO8oPCvm5RnJOrY--c09Pqy6KnUN4eaqJPa9HYShDI266rKB5Rm1Mp2Q96zmEy-UVz0G-e9dGzrp71H88aaujyvX89TN79i_wVWwFxBEq9ir991o9pzbH--X-1r6pHh30</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2640321688</pqid></control><display><type>article</type><title>Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Duarte, Sâmia Sousa ; Silva, Daiana Karla Frade ; Lisboa, Thaís Mangeon Honorato ; Gouveia, Rawny Galdino ; de Andrade, Camyla Caroliny Neves ; de Sousa, Valgrícia Matias ; Ferreira, Rafael Carlos ; de Moura, Ricardo Olimpio ; Gomes, Joilly Nilce Santana ; da Silva, Patricia Mirella ; de Lourdes Assunção Araújo de Azevedo, Fátima ; Keesen, Tatjana S. L. ; Gonçalves, Juan Carlos Ramos ; Batista, Leônia Maria ; Sobral, Marianna Vieira</creator><creatorcontrib>Duarte, Sâmia Sousa ; Silva, Daiana Karla Frade ; Lisboa, Thaís Mangeon Honorato ; Gouveia, Rawny Galdino ; de Andrade, Camyla Caroliny Neves ; de Sousa, Valgrícia Matias ; Ferreira, Rafael Carlos ; de Moura, Ricardo Olimpio ; Gomes, Joilly Nilce Santana ; da Silva, Patricia Mirella ; de Lourdes Assunção Araújo de Azevedo, Fátima ; Keesen, Tatjana S. L. ; Gonçalves, Juan Carlos Ramos ; Batista, Leônia Maria ; Sobral, Marianna Vieira</creatorcontrib><description>Background
Acridine compounds have been described as promising anticancer agents. Previous studies showed that (
E
)-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro.
Methods
MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125–200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC
50
) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide—PI—staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test.
Results
AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC
50
: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (
p
< 0.000001) and cell cycle arrest in S phase (
p
= 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (
p
< 0.000001) and late apoptotic cells (
p
< 0.000001). In addition, there was a reduction on ROS production (
p
< 0.000001).
Conclusions
AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.</description><identifier>ISSN: 1734-1140</identifier><identifier>EISSN: 2299-5684</identifier><identifier>DOI: 10.1007/s43440-022-00357-0</identifier><identifier>PMID: 35297003</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Acridines - pharmacology ; Antineoplastic Agents - pharmacology ; Antioxidants - pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms - drug therapy ; Drug Safety and Pharmacovigilance ; HCT116 Cells ; Humans ; Leukocytes, Mononuclear - metabolism ; Medicine ; Pharmacotherapy ; Pharmacy ; Reactive Oxygen Species - metabolism ; Short Communication ; Spiro Compounds - pharmacology</subject><ispartof>Pharmacological reports, 2022-06, Vol.74 (3), p.545-554</ispartof><rights>The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences 2022</rights><rights>2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-7817ed75cd20e34e410790a4a223c22c2bd47308afda31eaeaa9d8c1b729aa923</citedby><cites>FETCH-LOGICAL-c347t-7817ed75cd20e34e410790a4a223c22c2bd47308afda31eaeaa9d8c1b729aa923</cites><orcidid>0000-0002-7740-034X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s43440-022-00357-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s43440-022-00357-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35297003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duarte, Sâmia Sousa</creatorcontrib><creatorcontrib>Silva, Daiana Karla Frade</creatorcontrib><creatorcontrib>Lisboa, Thaís Mangeon Honorato</creatorcontrib><creatorcontrib>Gouveia, Rawny Galdino</creatorcontrib><creatorcontrib>de Andrade, Camyla Caroliny Neves</creatorcontrib><creatorcontrib>de Sousa, Valgrícia Matias</creatorcontrib><creatorcontrib>Ferreira, Rafael Carlos</creatorcontrib><creatorcontrib>de Moura, Ricardo Olimpio</creatorcontrib><creatorcontrib>Gomes, Joilly Nilce Santana</creatorcontrib><creatorcontrib>da Silva, Patricia Mirella</creatorcontrib><creatorcontrib>de Lourdes Assunção Araújo de Azevedo, Fátima</creatorcontrib><creatorcontrib>Keesen, Tatjana S. L.</creatorcontrib><creatorcontrib>Gonçalves, Juan Carlos Ramos</creatorcontrib><creatorcontrib>Batista, Leônia Maria</creatorcontrib><creatorcontrib>Sobral, Marianna Vieira</creatorcontrib><title>Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06</title><title>Pharmacological reports</title><addtitle>Pharmacol. Rep</addtitle><addtitle>Pharmacol Rep</addtitle><description>Background
Acridine compounds have been described as promising anticancer agents. Previous studies showed that (
E
)-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro.
Methods
MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125–200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC
50
) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide—PI—staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test.
Results
AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC
50
: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (
p
< 0.000001) and cell cycle arrest in S phase (
p
= 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (
p
< 0.000001) and late apoptotic cells (
p
< 0.000001). In addition, there was a reduction on ROS production (
p
< 0.000001).
Conclusions
AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.</description><subject>Acridines - pharmacology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Drug Safety and Pharmacovigilance</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Medicine</subject><subject>Pharmacotherapy</subject><subject>Pharmacy</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Short Communication</subject><subject>Spiro Compounds - pharmacology</subject><issn>1734-1140</issn><issn>2299-5684</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFPHCEYholpo1vtH-jBcPQg7ccHM8wcN5tWm9h4Wc-EBabBzMAIM4n-e7Fre-yBfASe9w08hHzh8JUDqG9FCimBASIDEI1icEI2iH3PmraTH8iGKyEZ5xLOyKdSHgEkR9GckjPRYK9qZkPidk7zkpZgqYmuriWk5-DqpH4YvF0KDZHe7va1p6U2jSnXQzNSa7INMU2GWj-OhR5eqKFlDjkxY3NwIfqKT3Nao7um21_77Y5Be0E-DmYs_vP7PCcPP77vd7fs7v7m5257x6yQamGq48o71ViH4IX0koPqwUiDKCyixYOTSkBnBmcE98Yb07vO8oPCvm5RnJOrY--c09Pqy6KnUN4eaqJPa9HYShDI266rKB5Rm1Mp2Q96zmEy-UVz0G-e9dGzrp71H88aaujyvX89TN79i_wVWwFxBEq9ir991o9pzbH--X-1r6pHh30</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Duarte, Sâmia Sousa</creator><creator>Silva, Daiana Karla Frade</creator><creator>Lisboa, Thaís Mangeon Honorato</creator><creator>Gouveia, Rawny Galdino</creator><creator>de Andrade, Camyla Caroliny Neves</creator><creator>de Sousa, Valgrícia Matias</creator><creator>Ferreira, Rafael Carlos</creator><creator>de Moura, Ricardo Olimpio</creator><creator>Gomes, Joilly Nilce Santana</creator><creator>da Silva, Patricia Mirella</creator><creator>de Lourdes Assunção Araújo de Azevedo, Fátima</creator><creator>Keesen, Tatjana S. L.</creator><creator>Gonçalves, Juan Carlos Ramos</creator><creator>Batista, Leônia Maria</creator><creator>Sobral, Marianna Vieira</creator><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7740-034X</orcidid></search><sort><creationdate>20220601</creationdate><title>Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06</title><author>Duarte, Sâmia Sousa ; Silva, Daiana Karla Frade ; Lisboa, Thaís Mangeon Honorato ; Gouveia, Rawny Galdino ; de Andrade, Camyla Caroliny Neves ; de Sousa, Valgrícia Matias ; Ferreira, Rafael Carlos ; de Moura, Ricardo Olimpio ; Gomes, Joilly Nilce Santana ; da Silva, Patricia Mirella ; de Lourdes Assunção Araújo de Azevedo, Fátima ; Keesen, Tatjana S. L. ; Gonçalves, Juan Carlos Ramos ; Batista, Leônia Maria ; Sobral, Marianna Vieira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-7817ed75cd20e34e410790a4a223c22c2bd47308afda31eaeaa9d8c1b729aa923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acridines - pharmacology</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Drug Safety and Pharmacovigilance</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Medicine</topic><topic>Pharmacotherapy</topic><topic>Pharmacy</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Short Communication</topic><topic>Spiro Compounds - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duarte, Sâmia Sousa</creatorcontrib><creatorcontrib>Silva, Daiana Karla Frade</creatorcontrib><creatorcontrib>Lisboa, Thaís Mangeon Honorato</creatorcontrib><creatorcontrib>Gouveia, Rawny Galdino</creatorcontrib><creatorcontrib>de Andrade, Camyla Caroliny Neves</creatorcontrib><creatorcontrib>de Sousa, Valgrícia Matias</creatorcontrib><creatorcontrib>Ferreira, Rafael Carlos</creatorcontrib><creatorcontrib>de Moura, Ricardo Olimpio</creatorcontrib><creatorcontrib>Gomes, Joilly Nilce Santana</creatorcontrib><creatorcontrib>da Silva, Patricia Mirella</creatorcontrib><creatorcontrib>de Lourdes Assunção Araújo de Azevedo, Fátima</creatorcontrib><creatorcontrib>Keesen, Tatjana S. L.</creatorcontrib><creatorcontrib>Gonçalves, Juan Carlos Ramos</creatorcontrib><creatorcontrib>Batista, Leônia Maria</creatorcontrib><creatorcontrib>Sobral, Marianna Vieira</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacological reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duarte, Sâmia Sousa</au><au>Silva, Daiana Karla Frade</au><au>Lisboa, Thaís Mangeon Honorato</au><au>Gouveia, Rawny Galdino</au><au>de Andrade, Camyla Caroliny Neves</au><au>de Sousa, Valgrícia Matias</au><au>Ferreira, Rafael Carlos</au><au>de Moura, Ricardo Olimpio</au><au>Gomes, Joilly Nilce Santana</au><au>da Silva, Patricia Mirella</au><au>de Lourdes Assunção Araújo de Azevedo, Fátima</au><au>Keesen, Tatjana S. L.</au><au>Gonçalves, Juan Carlos Ramos</au><au>Batista, Leônia Maria</au><au>Sobral, Marianna Vieira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06</atitle><jtitle>Pharmacological reports</jtitle><stitle>Pharmacol. Rep</stitle><addtitle>Pharmacol Rep</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>74</volume><issue>3</issue><spage>545</spage><epage>554</epage><pages>545-554</pages><issn>1734-1140</issn><eissn>2299-5684</eissn><abstract>Background
Acridine compounds have been described as promising anticancer agents. Previous studies showed that (
E
)-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro.
Methods
MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125–200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC
50
) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide—PI—staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test.
Results
AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC
50
: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (
p
< 0.000001) and cell cycle arrest in S phase (
p
= 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (
p
< 0.000001) and late apoptotic cells (
p
< 0.000001). In addition, there was a reduction on ROS production (
p
< 0.000001).
Conclusions
AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>35297003</pmid><doi>10.1007/s43440-022-00357-0</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7740-034X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1734-1140 |
| ispartof | Pharmacological reports, 2022-06, Vol.74 (3), p.545-554 |
| issn | 1734-1140 2299-5684 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2640321688 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Acridines - pharmacology Antineoplastic Agents - pharmacology Antioxidants - pharmacology Apoptosis Cell Line, Tumor Cell Proliferation Colorectal Neoplasms - drug therapy Drug Safety and Pharmacovigilance HCT116 Cells Humans Leukocytes, Mononuclear - metabolism Medicine Pharmacotherapy Pharmacy Reactive Oxygen Species - metabolism Short Communication Spiro Compounds - pharmacology |
| title | Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06 |
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