Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling
Casticin, a natural polymethoxyflavone isolated from A. annua, V. trifolia, and V. agnus‑castus induces apoptosis in cancer cells by activating FoxO3a. However, whether casticin inhibits in vitro carcinogenesis and cancer stem cell (CSC) characteristics, and whether casticin activates FoxO3a in smal...
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| Veröffentlicht in: | Oncology reports 2018-09, Vol.40 (3), p.1401-1410 |
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| creator | Gong, Qian Cao, Xiaozheng Cao, Jianguo Yang, Xiaohong Zeng, Wenbin |
| description | Casticin, a natural polymethoxyflavone isolated from A. annua, V. trifolia, and V. agnus‑castus induces apoptosis in cancer cells by activating FoxO3a. However, whether casticin inhibits in vitro carcinogenesis and cancer stem cell (CSC) characteristics, and whether casticin activates FoxO3a in small cell lung cancer (SCLC) cells remain unclear. We here demonstrated that casticin decreased sphere‑ and colony‑formation capabilities, and downregulated uPAR and CD133 in second‑generation spheres, which were considered as lung cancer stem‑like cells (LCSLCs), from SCLC H446 cells, in a concentration‑dependent manner. In addition, casticin dose‑dependently elevated the phosphorylation levels of AMPK and ACC, and reduced p‑FoxO3a expression. The above effects were attenuated by AMPK knockdown with small interfering RNAs (siRNAs). FoxO3a silencing resulted in decreased protein expression of FoxO3a, increased in vitro carcinogenesis and CSC characteristics, with no appreciable effects on AMPK and ACC phosphorylation, and displayed similar activities to those neutralizing the effects of casticin on in vitro carcinogenesis and CSC characteristics. These findings reveal a novel mechanism for regulating AMPK/FoxO3a signaling in response to casticin, suggesting a new strategy for SCLC therapy by targeting cancer stem‑like cells. |
| doi_str_mv | 10.3892/or.2018.6547 |
| format | Article |
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However, whether casticin inhibits in vitro carcinogenesis and cancer stem cell (CSC) characteristics, and whether casticin activates FoxO3a in small cell lung cancer (SCLC) cells remain unclear. We here demonstrated that casticin decreased sphere‑ and colony‑formation capabilities, and downregulated uPAR and CD133 in second‑generation spheres, which were considered as lung cancer stem‑like cells (LCSLCs), from SCLC H446 cells, in a concentration‑dependent manner. In addition, casticin dose‑dependently elevated the phosphorylation levels of AMPK and ACC, and reduced p‑FoxO3a expression. The above effects were attenuated by AMPK knockdown with small interfering RNAs (siRNAs). FoxO3a silencing resulted in decreased protein expression of FoxO3a, increased in vitro carcinogenesis and CSC characteristics, with no appreciable effects on AMPK and ACC phosphorylation, and displayed similar activities to those neutralizing the effects of casticin on in vitro carcinogenesis and CSC characteristics. These findings reveal a novel mechanism for regulating AMPK/FoxO3a signaling in response to casticin, suggesting a new strategy for SCLC therapy by targeting cancer stem‑like cells.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2018.6547</identifier><identifier>PMID: 30015975</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Apoptosis ; Breast cancer ; Care and treatment ; Cell culture ; Cell cycle ; Cell growth ; Cellular signal transduction ; Development and progression ; Flavonoids ; Gene expression ; Genetic aspects ; Health aspects ; Kinases ; Lung cancer ; Medical prognosis ; Ovarian cancer ; Penicillin ; Phosphorylation ; Protein expression ; Proteins ; Small cell lung cancer ; Spheres ; Stem cells ; Transcription factors ; Tumors</subject><ispartof>Oncology reports, 2018-09, Vol.40 (3), p.1401-1410</ispartof><rights>COPYRIGHT 2018 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-c025d23200c9c3b96736bc4a01373ed35805d65bc6550c1721a33fe3871e03423</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30015975$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gong, Qian</creatorcontrib><creatorcontrib>Cao, Xiaozheng</creatorcontrib><creatorcontrib>Cao, Jianguo</creatorcontrib><creatorcontrib>Yang, Xiaohong</creatorcontrib><creatorcontrib>Zeng, Wenbin</creatorcontrib><title>Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Casticin, a natural polymethoxyflavone isolated from A. annua, V. trifolia, and V. agnus‑castus induces apoptosis in cancer cells by activating FoxO3a. However, whether casticin inhibits in vitro carcinogenesis and cancer stem cell (CSC) characteristics, and whether casticin activates FoxO3a in small cell lung cancer (SCLC) cells remain unclear. We here demonstrated that casticin decreased sphere‑ and colony‑formation capabilities, and downregulated uPAR and CD133 in second‑generation spheres, which were considered as lung cancer stem‑like cells (LCSLCs), from SCLC H446 cells, in a concentration‑dependent manner. In addition, casticin dose‑dependently elevated the phosphorylation levels of AMPK and ACC, and reduced p‑FoxO3a expression. The above effects were attenuated by AMPK knockdown with small interfering RNAs (siRNAs). FoxO3a silencing resulted in decreased protein expression of FoxO3a, increased in vitro carcinogenesis and CSC characteristics, with no appreciable effects on AMPK and ACC phosphorylation, and displayed similar activities to those neutralizing the effects of casticin on in vitro carcinogenesis and CSC characteristics. These findings reveal a novel mechanism for regulating AMPK/FoxO3a signaling in response to casticin, suggesting a new strategy for SCLC therapy by targeting cancer stem‑like cells.</description><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cellular signal transduction</subject><subject>Development and progression</subject><subject>Flavonoids</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Medical prognosis</subject><subject>Ovarian cancer</subject><subject>Penicillin</subject><subject>Phosphorylation</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Small cell lung cancer</subject><subject>Spheres</subject><subject>Stem cells</subject><subject>Transcription factors</subject><subject>Tumors</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkc1r3DAQxU1paNK0t56LoNBTvRlpJH8cl6VpShOSQwu9Ca0sexVsaaux0-a_j92kH4EgGInH7w2jeVn2hsMKq1qcxLQSwKtVoWT5LDviZc1zIZE_n98geI6ovh9mL4muAUQJRf0iO0QArupSHWU_N4ZGb31gNO33yRE5YuPOMWvSrMbOBUeeWGwZDabvmXVz6afQzUSwLrEzKYvf6uJLcep2zNjR35jRx7D41hdXX05O469LNIx8F0zvQ_cqO2hNT-71w32cfTv9-HVzlp9ffvq8WZ_nVio15haEagQKAFtb3NZFicXWSgMcS3QNqgpUU6itLZQCy0vBDWLrsCq5A5QCj7N39333Kf6YHI36Ok5pnoG0gFqhrLmCf1Rneqd9aOOYjB08Wb1WSoLkFSzU6glqPo0bvI3BtX7WHxne_2fYOdOPO4r9tGyGHoMf7kGbIlFyrd4nP5h0qznoJWUdk15S1kvKM_724VPTdnDNX_hPrHgHXimeww</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Gong, Qian</creator><creator>Cao, Xiaozheng</creator><creator>Cao, Jianguo</creator><creator>Yang, Xiaohong</creator><creator>Zeng, Wenbin</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20180901</creationdate><title>Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling</title><author>Gong, Qian ; 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However, whether casticin inhibits in vitro carcinogenesis and cancer stem cell (CSC) characteristics, and whether casticin activates FoxO3a in small cell lung cancer (SCLC) cells remain unclear. We here demonstrated that casticin decreased sphere‑ and colony‑formation capabilities, and downregulated uPAR and CD133 in second‑generation spheres, which were considered as lung cancer stem‑like cells (LCSLCs), from SCLC H446 cells, in a concentration‑dependent manner. In addition, casticin dose‑dependently elevated the phosphorylation levels of AMPK and ACC, and reduced p‑FoxO3a expression. The above effects were attenuated by AMPK knockdown with small interfering RNAs (siRNAs). FoxO3a silencing resulted in decreased protein expression of FoxO3a, increased in vitro carcinogenesis and CSC characteristics, with no appreciable effects on AMPK and ACC phosphorylation, and displayed similar activities to those neutralizing the effects of casticin on in vitro carcinogenesis and CSC characteristics. These findings reveal a novel mechanism for regulating AMPK/FoxO3a signaling in response to casticin, suggesting a new strategy for SCLC therapy by targeting cancer stem‑like cells.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>30015975</pmid><doi>10.3892/or.2018.6547</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Breast cancer Care and treatment Cell culture Cell cycle Cell growth Cellular signal transduction Development and progression Flavonoids Gene expression Genetic aspects Health aspects Kinases Lung cancer Medical prognosis Ovarian cancer Penicillin Phosphorylation Protein expression Proteins Small cell lung cancer Spheres Stem cells Transcription factors Tumors |
| title | Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling |
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