Network pharmacology analysis and experimental verification of the antitumor effect and molecular mechanism of isocryptomerin on HepG2 cells
Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay reve...
Saved in:
| Published in | Drug development research Vol. 85; no. 2; pp. e22165 - n/a |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wiley Subscription Services, Inc
01.04.2024
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria‐dependent apoptosis through the Bad/cyto‐c/cleaved (cle)‐caspase‐3/cleaved (cle)‐PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen‐activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p‐p38 and p‐JNK expression and decreasing p‐EGFR, p‐SRC, p‐ERK, and p‐STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p‐AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p‐GSK‐3β, β‐catenin, and N‐cadherin expression and increasing E‐cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO‐induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N‐acetyl‐
l‐cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS‐mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells. |
|---|---|
| AbstractList | Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine
Selaginellae
Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria‐dependent apoptosis through the Bad/cyto‐c/cleaved (cle)‐caspase‐3/cleaved (cle)‐PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen‐activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p‐p38 and p‐JNK expression and decreasing p‐EGFR, p‐SRC, p‐ERK, and p‐STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p‐AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p‐GSK‐3β, β‐catenin, and N‐cadherin expression and increasing E‐cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO‐induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N‐acetyl‐
l
‐cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS‐mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells. Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria‐dependent apoptosis through the Bad/cyto‐c/cleaved (cle)‐caspase‐3/cleaved (cle)‐PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen‐activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p‐p38 and p‐JNK expression and decreasing p‐EGFR, p‐SRC, p‐ERK, and p‐STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p‐AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p‐GSK‐3β, β‐catenin, and N‐cadherin expression and increasing E‐cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO‐induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N‐acetyl‐l‐cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS‐mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells. Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria‐dependent apoptosis through the Bad/cyto‐c/cleaved (cle)‐caspase‐3/cleaved (cle)‐PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen‐activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p‐p38 and p‐JNK expression and decreasing p‐EGFR, p‐SRC, p‐ERK, and p‐STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p‐AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p‐GSK‐3β, β‐catenin, and N‐cadherin expression and increasing E‐cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO‐induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N‐acetyl‐ l‐cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS‐mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells. Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria-dependent apoptosis through the Bad/cyto-c/cleaved (cle)-caspase-3/cleaved (cle)-PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p-p38 and p-JNK expression and decreasing p-EGFR, p-SRC, p-ERK, and p-STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p-AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p-GSK-3β, β-catenin, and N-cadherin expression and increasing E-cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO-induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N-acetyl- l-cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS-mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells.Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria-dependent apoptosis through the Bad/cyto-c/cleaved (cle)-caspase-3/cleaved (cle)-PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p-p38 and p-JNK expression and decreasing p-EGFR, p-SRC, p-ERK, and p-STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p-AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p-GSK-3β, β-catenin, and N-cadherin expression and increasing E-cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO-induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N-acetyl- l-cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS-mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells. Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria-dependent apoptosis through the Bad/cyto-c/cleaved (cle)-caspase-3/cleaved (cle)-PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p-p38 and p-JNK expression and decreasing p-EGFR, p-SRC, p-ERK, and p-STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p-AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p-GSK-3β, β-catenin, and N-cadherin expression and increasing E-cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO-induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N-acetyl- l-cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS-mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells. |
| Author | Cao, Jing‐Long Tang, Yan‐Jun Jin, Cheng‐Hao Hou, Wen‐Shuang Li, Tian‐Zhu Wang, An‐Qi Li, Shu‐Mei |
| Author_xml | – sequence: 1 givenname: Jing‐Long surname: Cao fullname: Cao, Jing‐Long organization: Heilongjiang Bayi Agricultural University – sequence: 2 givenname: Shu‐Mei surname: Li fullname: Li, Shu‐Mei organization: Daqing Oilfield General Hospital – sequence: 3 givenname: Yan‐Jun surname: Tang fullname: Tang, Yan‐Jun organization: Heilongjiang Bayi Agricultural University – sequence: 4 givenname: Wen‐Shuang surname: Hou fullname: Hou, Wen‐Shuang organization: Heilongjiang Bayi Agricultural University – sequence: 5 givenname: An‐Qi surname: Wang fullname: Wang, An‐Qi organization: Heilongjiang Bayi Agricultural University – sequence: 6 givenname: Tian‐Zhu surname: Li fullname: Li, Tian‐Zhu email: litianzhu@cfxy.edu.cn organization: Chifeng University – sequence: 7 givenname: Cheng‐Hao orcidid: 0000-0003-4431-2623 surname: Jin fullname: Jin, Cheng‐Hao email: jinchenghao3727@qq.com organization: National Coarse Cereals Engineering Research Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38400652$$D View this record in MEDLINE/PubMed |
| BookMark | eNp10cFu1DAQBmALFdFt4cALIEtc4JDWHju7yRG10CJVICE4W15nzLrYcbAdSt6Bh8bbLRyQOHlkfTMazX9CjsY4IiHPOTvjjMH5MKQzAL5uH5EVZ33XAPT9EVkx2EAjRc-PyUnOt4xxLrvuCTkWnWRs3cKK_PqA5S6mb3Ta6RS0iT5-XagetV-yy7UYKP6cMLmAY9Ge_qildUYXF0caLS07rKi4MoeYKFqLptx3hejRzF4nGtDs9Ohy2HuXo0nLVGKog-qEkV7jdAXUoPf5KXlstc_47OE9JV_evf18cd3cfLx6f_HmpjGCi7ZBqfW2a7dgW2k6MD0OnLWWcwbSSskGY4xk0loDHKyxw1prLgwfWP2BDROn5NVh7pTi9xlzUcHl_QZ6xDhnBb0AxntoN5W-_IfexjnV82QlmOgEiI3sq3rxoOZtwEFN9V46LerPnSt4fQAmxZwT2r-EM7XPUNUM1X2G1Z4f7J3zuPwfqsvLT4eO31hjn04 |
| Cites_doi | 10.3390/ijms21061960 10.1111/cas.13598 10.1155/2019/4745132 10.1016/j.bbrc.2021.11.101 10.1111/cbdd.13933 10.1042/BSR20180992 10.1007/s00210-019-01763-7 10.3390/ijms222312880 10.1046/j.1365-2184.2000.00191.x 10.1016/j.bbrc.2008.12.030 10.3390/ijms221910637 10.1016/j.phymed.2021.153807 10.3390/ijms21165598 10.3748/wjg.v27.i20.2434 10.1159/000508337 10.55782/ane-2022-022 10.1007/s11033-018-4294-5 10.1038/cddis.2017.422 10.1155/2011/567305 10.1016/j.bbamcr.2020.118659 10.3389/fmicb.2017.01118 10.3892/mmr.2014.2736 10.5582/bst.2021.01094 10.1080/01480545.2019.1658767 10.1016/j.biopha.2020.111044 10.1016/j.cellsig.2019.03.004 10.3390/molecules27092946 10.3390/cells9061370 10.4103/ijpvm.IJPVM_11_20 10.1038/s41568-021-00435-0 10.1016/bs.acr.2020.10.001 10.1042/BSR20201807 10.1186/s13045-022-01248-w 10.1038/s41571-020-0341-y 10.3390/cancers12082266 10.1155/2021/8900122 10.52586/4994 10.1016/S0140-6736(22)01200-4 10.1016/j.biopha.2019.109772 10.1016/j.lfs.2022.120804 10.1016/bs.acr.2020.02.002 10.1590/1519-6984.228437 10.18632/oncotarget.3999 10.1016/0031-9422(95)00212-p 10.3892/mmr.2020.11046 10.1007/978-3-030-42667-5_1 10.1016/j.tcb.2021.07.001 10.1007/s13277-016-5257-x |
| ContentType | Journal Article |
| Copyright | 2024 Wiley Periodicals LLC. |
| Copyright_xml | – notice: 2024 Wiley Periodicals LLC. |
| DBID | AAYXX CITATION NPM 7QO 7QP 7QR 7TK 7U7 8FD C1K FR3 K9. P64 7X8 |
| DOI | 10.1002/ddr.22165 |
| DatabaseName | CrossRef PubMed Biotechnology Research Abstracts Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Neurosciences Abstracts Toxicology Abstracts Technology Research Database Environmental Sciences and Pollution Management Engineering Research Database ProQuest Health & Medical Complete (Alumni) Biotechnology and BioEngineering Abstracts MEDLINE - Academic |
| DatabaseTitle | CrossRef PubMed Biotechnology Research Abstracts Technology Research Database Toxicology Abstracts ProQuest Health & Medical Complete (Alumni) Chemoreception Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts Environmental Sciences and Pollution Management MEDLINE - Academic |
| DatabaseTitleList | CrossRef Biotechnology Research Abstracts MEDLINE - Academic PubMed |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1098-2299 |
| EndPage | n/a |
| ExternalDocumentID | 38400652 10_1002_ddr_22165 DDR22165 |
| Genre | researchArticle Journal Article |
| GrantInformation_xml | – fundername: Central Government Supports Local College Reform and Development Fund Talent Training Project funderid: 2020GSP16 – fundername: Heilongjiang Province Key Research and Development Plan Guidance Project funderid: GZ20220039 – fundername: Postgraduate Innovative Research Project of Heilongjiang Bayi Agricultural University funderid: YJSCX2022‐Y55 – fundername: Heilongjiang Touyan Innovation Team Program funderid: 2019HTY078 – fundername: Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region funderid: NJYT24032 – fundername: National Natural Science Foundation of China funderid: 82060118 – fundername: Central Government Supports Local College Reform and Development Fund Talent Training Project grantid: 2020GSP16 – fundername: Postgraduate Innovative Research Project of Heilongjiang Bayi Agricultural University grantid: YJSCX2022-Y55 – fundername: National Natural Science Foundation of China grantid: 82060118 – fundername: Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region grantid: NJYT24032 – fundername: Heilongjiang Touyan Innovation Team Program grantid: 2019HTY078 – fundername: Heilongjiang Province Key Research and Development Plan Guidance Project grantid: GZ20220039 |
| GroupedDBID | --- .3N .GA .GJ .Y3 05W 0R~ 10A 1L6 1OB 1OC 1ZS 31~ 33P 3SF 3WU 4.4 4ZD 50Y 50Z 51W 51X 52M 52N 52O 52P 52S 52T 52U 52W 52X 53G 5GY 5RE 5VS 66C 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A03 AAESR AAEVG AAHHS AAHQN AAMNL AANHP AANLZ AAONW AASGY AAXRX AAYCA AAZKR ABCQN ABCUV ABEML ABIJN ABJNI ABPVW ACAHQ ACBWZ ACCFJ ACCZN ACGFS ACIWK ACPOU ACPRK ACRPL ACSCC ACXBN ACXQS ACYXJ ADBBV ADEOM ADIZJ ADKYN ADMGS ADNMO ADOZA ADXAS ADZMN ADZOD AEEZP AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFFPM AFGKR AFPWT AFRAH AFWVQ AFZJQ AHBTC AITYG AIURR AIWBW AJBDE AJXKR ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN ALVPJ AMBMR AMYDB ASPBG ATUGU AUFTA AVWKF AZBYB AZFZN AZVAB BAFTC BDRZF BFHJK BHBCM BMNLL BMXJE BNHUX BROTX BRXPI BY8 CS3 D-E D-F DCZOG DPXWK DR1 DR2 DRFUL DRSTM DU5 EBD EBS EJD EMOBN F00 F01 F04 F5P FEDTE G-S G.N GNP GODZA GWYGA H.T H.X HF~ HGLYW HHY HHZ HVGLF HZ~ IX1 J0M JPC KQQ LATKE LAW LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LSO LUTES LW6 LYRES M6M MEWTI MK4 MRFUL MRSTM MSFUL MSSTM MXFUL MXSTM N04 N05 N9A NF~ O66 O9- OIG OVD P2P P2W P2X P4D PALCI Q.N Q11 QB0 QRW R.K RIWAO RJQFR ROL RWD RWI RX1 RYL SAMSI SUPJJ SV3 TEORI UB1 V2E W8V W99 WBKPD WHWMO WIB WIH WIK WJL WOHZO WQJ WRC WUP WVDHM WXSBR XG1 XV2 ZGI ZXP ZZTAW ~IA ~WT AAYXX AEYWJ AGHNM AGQPQ AGYGG CITATION NPM VXZ 7QO 7QP 7QR 7TK 7U7 8FD AAMMB AEFGJ AGXDD AIDQK AIDYY C1K FR3 K9. P64 7X8 |
| ID | FETCH-LOGICAL-c3135-e4aab85b2f54c82c9ed105f11024f440dccc404ffc212fcfd6aa13c1d0fc22703 |
| IEDL.DBID | DR2 |
| ISSN | 0272-4391 1098-2299 |
| IngestDate | Fri Jul 11 03:00:50 EDT 2025 Sun Jul 13 04:24:04 EDT 2025 Wed Feb 19 02:07:10 EST 2025 Tue Jul 01 02:47:05 EDT 2025 Wed Jan 22 17:19:43 EST 2025 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | isocryptomerin cell cycle ROS cell apoptosis cell migration EGFR hepatocellular carcinoma |
| Language | English |
| License | 2024 Wiley Periodicals LLC. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c3135-e4aab85b2f54c82c9ed105f11024f440dccc404ffc212fcfd6aa13c1d0fc22703 |
| Notes | Jing‐Long Cao, Shu‐Mei Li, and Yan‐Jun Tang contributed equally to this study as first authors. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0003-4431-2623 |
| PMID | 38400652 |
| PQID | 3038323749 |
| PQPubID | 866385 |
| PageCount | 14 |
| ParticipantIDs | proquest_miscellaneous_2932019257 proquest_journals_3038323749 pubmed_primary_38400652 crossref_primary_10_1002_ddr_22165 wiley_primary_10_1002_ddr_22165_DDR22165 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | April 2024 2024-04-00 2024-Apr 20240401 |
| PublicationDateYYYYMMDD | 2024-04-01 |
| PublicationDate_xml | – month: 04 year: 2024 text: April 2024 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Hoboken |
| PublicationTitle | Drug development research |
| PublicationTitleAlternate | Drug Dev Res |
| PublicationYear | 2024 |
| Publisher | Wiley Subscription Services, Inc |
| Publisher_xml | – name: Wiley Subscription Services, Inc |
| References | 2021; 27 2017; 8 2019; 2019 2021; 26 2015; 6 2020; 1260 2021; 22 2020; 40 2021; 149 2015; 11 2019; 59 2020; 17 2020; 148 2022; 45 2019; 39 2020; 122 2020; 12 2018; 109 2022; 22 2018; 45 2016; 37 2022; 27 2009; 379 2011; 2011 1995; 40 2021; 15 2021; 98 2021; 12 2020; 393 2022; 82 2000; 33 2020; 9 2020; 1867 2022; 15 2022; 96 2022; 32 2021; 133 2020; 21 2020; 87 2022; 306 2021; 2021 2021; 81 2022; 400 2022; 587 e_1_2_9_30_1 e_1_2_9_31_1 e_1_2_9_11_1 e_1_2_9_34_1 e_1_2_9_10_1 e_1_2_9_35_1 e_1_2_9_13_1 e_1_2_9_32_1 e_1_2_9_12_1 e_1_2_9_33_1 e_1_2_9_15_1 e_1_2_9_38_1 e_1_2_9_14_1 e_1_2_9_39_1 e_1_2_9_17_1 e_1_2_9_36_1 e_1_2_9_16_1 e_1_2_9_37_1 e_1_2_9_19_1 e_1_2_9_18_1 e_1_2_9_41_1 e_1_2_9_42_1 e_1_2_9_20_1 e_1_2_9_40_1 e_1_2_9_22_1 e_1_2_9_45_1 e_1_2_9_21_1 e_1_2_9_46_1 e_1_2_9_24_1 e_1_2_9_43_1 e_1_2_9_23_1 e_1_2_9_44_1 e_1_2_9_8_1 e_1_2_9_7_1 e_1_2_9_6_1 e_1_2_9_5_1 e_1_2_9_4_1 e_1_2_9_3_1 e_1_2_9_2_1 e_1_2_9_9_1 e_1_2_9_26_1 e_1_2_9_49_1 e_1_2_9_25_1 e_1_2_9_28_1 e_1_2_9_47_1 e_1_2_9_27_1 e_1_2_9_48_1 e_1_2_9_29_1 |
| References_xml | – volume: 12 year: 2020 article-title: mTOR inhibition leads to Src‐mediated EGFR internalisation and degradation in glioma cells publication-title: Cancers – volume: 12 start-page: 64 year: 2021 article-title: Investigation of the effect of 5‐Aza‐2’‐deoxycytidine in comparison to and in combination with trichostatin A on p16INK4a, p14ARF, p15INK4b gene expression, cell growth inhibition and apoptosis induction in colon cancer Caco‐2 cell line publication-title: International Journal of Preventive Medicine – volume: 400 start-page: 1345 year: 2022 end-page: 1362 article-title: Hepatocellular carcinoma publication-title: The Lancet – volume: 32 start-page: 30 year: 2022 end-page: 44 article-title: Cell cycle on the crossroad of tumorigenesis and cancer therapy publication-title: Trends in Cell Biology – volume: 33 start-page: 261 year: 2000 end-page: 274 article-title: Cell cycle checkpoints and their inactivation in human cancer publication-title: Cell Proliferation – volume: 122 year: 2020 article-title: Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src‐mediated NF‐κB p65 and MAPK signaling pathways in septic AKI mice publication-title: Biomedicine & Pharmacotherapy – volume: 2011 start-page: 1 year: 2011 end-page: 6 article-title: E‐cadherin/β‐catenin complex and the epithelial barrier publication-title: Journal of Biomedicine and Biotechnology – volume: 1260 start-page: 1 year: 2020 end-page: 12 article-title: Targeting ROS‐mediated crosstalk between autophagy and apoptosis in cancer publication-title: Advances in Experimental Medicine and Biology – volume: 22 year: 2021 article-title: Donepezil regulates LPS and Aβ‐stimulated neuroinflammation through MAPK/NLRP3 inflammasome/STAT3 signaling publication-title: International Journal of Molecular Sciences – volume: 22 year: 2021 article-title: Revisiting hepatic artery infusion chemotherapy in the treatment of advanced hepatocellular carcinoma publication-title: International Journal of Molecular Sciences – volume: 133 year: 2021 article-title: Anticancer activities of TCM and their active components against tumor metastasis publication-title: Biomedicine & Pharmacotherapy=Biomédecine & pharmacothérapie – volume: 9 year: 2020 article-title: Biomarkers in hepatocellular carcinoma: Diagnosis, prognosis and treatment response assessment publication-title: Cells – volume: 21 year: 2020 article-title: The significance of mitochondrial dysfunction in cancer publication-title: International Journal of Molecular Sciences – volume: 45 start-page: 1339 year: 2018 end-page: 1348 article-title: A natural flavonoid lawsonaringenin induces cell cycle arrest and apoptosis in HT‐29 colorectal cancer cells by targeting multiple signalling pathways publication-title: Molecular Biology Reports – volume: 37 start-page: 13545 year: 2016 end-page: 13555 article-title: Investigation of N‐cadherin/β‐catenin expression in adrenocortical tumors publication-title: Tumor Biology – volume: 11 start-page: 712 year: 2015 end-page: 718 article-title: Reactive oxygen species‐mediated activation of the Src‐epidermal growth factor receptor‐Akt signaling cascade prevents bortezomib‐induced apoptosis in hepatocellular carcinoma cells publication-title: Molecular Medicine Reports – volume: 22 start-page: 280 year: 2022 end-page: 297 article-title: The role of ROS in tumour development and progression publication-title: Nature Reviews Cancer – volume: 8 year: 2017 article-title: Cell cycle‐dependent expression dynamics of G1/S specific cyclin, cellulose synthase and cellulase in the dinoflagellate prorocentrum donghaiense publication-title: Frontiers in Microbiology – volume: 1867 year: 2020 article-title: GSK‐3β in DNA repair, apoptosis, and resistance of chemotherapy, radiotherapy of cancer publication-title: Biochimica et Biophysica Acta (BBA)‐Molecular Cell Research – volume: 45 start-page: 33 year: 2022 end-page: 43 article-title: 2‐(Naphthalene‐2‐thio)‐5,8‐dimethoxy‐1,4‐naphthoquinone induces apoptosis via ROS‐mediated MAPK, AKT, and STAT3 signaling pathways in HepG2 human hepatocellular carcinoma cells publication-title: Drug and Chemical Toxicology – volume: 15 start-page: 138 year: 2021 end-page: 141 article-title: Surgical treatment of hepatocellular carcinoma publication-title: BioScience Trends – volume: 587 start-page: 99 year: 2022 end-page: 106 article-title: Auriculasin enhances ROS generation to regulate colorectal cancer cell apoptosis, ferroptosis, oxeiptosis, invasion and colony formation publication-title: Biochemical and Biophysical Research Communications – volume: 8 year: 2017 article-title: Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL‐2 signaling in osteosarcoma publication-title: Cell Death & Disease – volume: 39 year: 2019 article-title: Apoptosis and apoptotic body: Disease message and therapeutic target potentials publication-title: Bioscience Reports – volume: 17 start-page: 395 year: 2020 end-page: 417 article-title: Targeting apoptosis in cancer therapy publication-title: Nature Reviews Clinical Oncology – volume: 379 start-page: 676 year: 2009 end-page: 680 article-title: Isocryptomerin, a novel membrane‐active antifungal compound from publication-title: Biochemical and Biophysical Research Communications – volume: 21 year: 2020 article-title: The roles of cyclin‐dependent kinases in cell‐cycle progression and therapeutic strategies in human breast cancer publication-title: International Journal of Molecular Sciences – volume: 21 start-page: 2321 year: 2020 end-page: 2334 article-title: Baicalin alleviates bleomycin‑induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway publication-title: Molecular Medicine Reports – volume: 148 start-page: 147 year: 2020 end-page: 169 article-title: Cyclin D‐CDK 4/6 functions in cancer publication-title: Advances in Cancer Research – volume: 109 start-page: 1414 year: 2018 end-page: 1427 article-title: PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K/Akt/GSK‐3β/Snail signaling publication-title: Cancer Science – volume: 2021 start-page: 1 year: 2021 end-page: 9 article-title: Mitochondrial mechanisms of apoptosis and necroptosis in liver diseases publication-title: Analytical Cellular Pathology – volume: 81 start-page: 1133 year: 2021 end-page: 1143 article-title: Apoptosis (programmed cell death) and its signals: A review publication-title: Brazilian Journal of Biology – volume: 26 start-page: 873 year: 2021 end-page: 881 article-title: Comparative safety and efficacy of molecular‐targeted drugs, immune checkpoint inhibitors, hepatic arterial infusion chemotherapy and their combinations in advanced hepatocellular carcinoma: Findings from advances in landmark trials publication-title: Frontiers in Bioscience‐Landmark – volume: 306 year: 2022 article-title: Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1‐mediated modulation of PI3K/AKT/GSK‐3β signaling publication-title: Life Sciences – volume: 82 start-page: 237 year: 2022 end-page: 243 article-title: TFF3 promotes pituitary tumor cell migration and angiogenesis via VEGFA publication-title: Acta Neurobiologiae Experimentalis – volume: 40 year: 2020 article-title: Tanshinone IIA induces ferroptosis in gastric cancer cells through p53‐mediated SLC7A11 down‐regulation publication-title: Bioscience Reports – volume: 2019 start-page: 1 year: 2019 end-page: 11 article-title: Sirt5 attenuates cisplatin‐induced acute kidney injury through regulation of Nrf2/HO‐1 and Bcl‐2 publication-title: BioMed Research International – volume: 6 start-page: 39521 year: 2015 end-page: 39537 article-title: Novel agents for advanced pancreatic cancer publication-title: Oncotarget – volume: 59 start-page: 1 year: 2019 end-page: 12 article-title: SLFN5 suppresses cancer cell migration and invasion by inhibiting MT1‐MMP expression via AKT/GSK‐3β/β‐catenin pathway publication-title: Cellular Signalling – volume: 15 start-page: 32 year: 2022 article-title: Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF/miR‐192‐5p/CYR61/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment publication-title: Journal of Hematology & Oncology – volume: 98 start-page: 779 year: 2021 end-page: 786 article-title: The flavonoid Astragalin shows anti‐tumor activity and inhibits PI3K/AKT signaling in gastric cancer publication-title: Chemical Biology & Drug Design – volume: 40 start-page: 129 year: 1995 end-page: 134 article-title: Cytotoxic biflavonoids from publication-title: Phytochemistry – volume: 27 year: 2022 article-title: Atractylodin induces apoptosis and inhibits the migration of A549 lung cancer cells by regulating ROS‐mediated signaling pathways publication-title: Molecules – volume: 149 start-page: 1 year: 2021 end-page: 61 article-title: Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification publication-title: Advances in Cancer Research – volume: 87 start-page: 218 year: 2020 end-page: 231 article-title: Molecular complexity of lymphovascular invasion: The role of cell migration in breast cancer as a prototype publication-title: Pathobiology – volume: 27 start-page: 2434 year: 2021 end-page: 2457 article-title: Role of modern radiotherapy in managing patients with hepatocellular carcinoma publication-title: World Journal of Gastroenterology – volume: 96 year: 2022 article-title: Agrimoniin sensitizes pancreatic cancer to apoptosis through ROS‐mediated energy metabolism dysfunction publication-title: Phytomedicine – volume: 393 start-page: 1987 year: 2020 end-page: 1999 article-title: Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma cells via the ROS‐mediated MAPK/AKT/NF‐κB signaling pathway publication-title: Naunyn‐Schmiedeberg's Archives of Pharmacology – ident: e_1_2_9_12_1 doi: 10.3390/ijms21061960 – ident: e_1_2_9_17_1 doi: 10.1111/cas.13598 – ident: e_1_2_9_25_1 doi: 10.1155/2019/4745132 – ident: e_1_2_9_40_1 doi: 10.1016/j.bbrc.2021.11.101 – ident: e_1_2_9_44_1 doi: 10.1111/cbdd.13933 – ident: e_1_2_9_45_1 doi: 10.1042/BSR20180992 – ident: e_1_2_9_41_1 doi: 10.1007/s00210-019-01763-7 – ident: e_1_2_9_6_1 doi: 10.3390/ijms222312880 – ident: e_1_2_9_27_1 doi: 10.1046/j.1365-2184.2000.00191.x – ident: e_1_2_9_20_1 doi: 10.1016/j.bbrc.2008.12.030 – ident: e_1_2_9_19_1 doi: 10.3390/ijms221910637 – ident: e_1_2_9_49_1 doi: 10.1016/j.phymed.2021.153807 – ident: e_1_2_9_26_1 doi: 10.3390/ijms21165598 – ident: e_1_2_9_7_1 doi: 10.3748/wjg.v27.i20.2434 – ident: e_1_2_9_18_1 doi: 10.1159/000508337 – ident: e_1_2_9_43_1 doi: 10.55782/ane-2022-022 – ident: e_1_2_9_3_1 doi: 10.1007/s11033-018-4294-5 – ident: e_1_2_9_23_1 doi: 10.1038/cddis.2017.422 – ident: e_1_2_9_37_1 doi: 10.1155/2011/567305 – ident: e_1_2_9_21_1 doi: 10.1016/j.bbamcr.2020.118659 – ident: e_1_2_9_34_1 doi: 10.3389/fmicb.2017.01118 – ident: e_1_2_9_16_1 doi: 10.3892/mmr.2014.2736 – ident: e_1_2_9_36_1 doi: 10.5582/bst.2021.01094 – ident: e_1_2_9_24_1 doi: 10.1080/01480545.2019.1658767 – ident: e_1_2_9_42_1 doi: 10.1016/j.biopha.2020.111044 – ident: e_1_2_9_39_1 doi: 10.1016/j.cellsig.2019.03.004 – ident: e_1_2_9_47_1 doi: 10.3390/molecules27092946 – ident: e_1_2_9_30_1 doi: 10.3390/cells9061370 – ident: e_1_2_9_33_1 doi: 10.4103/ijpvm.IJPVM_11_20 – ident: e_1_2_9_8_1 doi: 10.1038/s41568-021-00435-0 – ident: e_1_2_9_9_1 doi: 10.1016/bs.acr.2020.10.001 – ident: e_1_2_9_15_1 doi: 10.1042/BSR20201807 – ident: e_1_2_9_46_1 doi: 10.1186/s13045-022-01248-w – ident: e_1_2_9_5_1 doi: 10.1038/s41571-020-0341-y – ident: e_1_2_9_11_1 doi: 10.3390/cancers12082266 – ident: e_1_2_9_10_1 doi: 10.1155/2021/8900122 – ident: e_1_2_9_29_1 doi: 10.52586/4994 – ident: e_1_2_9_38_1 doi: 10.1016/S0140-6736(22)01200-4 – ident: e_1_2_9_31_1 doi: 10.1016/j.biopha.2019.109772 – ident: e_1_2_9_4_1 doi: 10.1016/j.lfs.2022.120804 – ident: e_1_2_9_14_1 doi: 10.1016/bs.acr.2020.02.002 – ident: e_1_2_9_28_1 doi: 10.1590/1519-6984.228437 – ident: e_1_2_9_2_1 doi: 10.18632/oncotarget.3999 – ident: e_1_2_9_35_1 doi: 10.1016/0031-9422(95)00212-p – ident: e_1_2_9_48_1 doi: 10.3892/mmr.2020.11046 – ident: e_1_2_9_13_1 doi: 10.1007/978-3-030-42667-5_1 – ident: e_1_2_9_22_1 doi: 10.1016/j.tcb.2021.07.001 – ident: e_1_2_9_32_1 doi: 10.1007/s13277-016-5257-x |
| SSID | ssj0011488 |
| Score | 2.3768482 |
| Snippet | Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study... Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study... |
| SourceID | proquest pubmed crossref wiley |
| SourceType | Aggregation Database Index Database Publisher |
| StartPage | e22165 |
| SubjectTerms | AKT protein Anticancer properties Antitumor activity Apoptosis Caspase Cell adhesion & migration cell apoptosis Cell cycle Cell migration Cell viability Cyclin D Cyclin-dependent kinase inhibitor p27 EGFR Epidermal growth factor receptors Flavonoids G1 phase Growth factors Hepatocellular carcinoma isocryptomerin Kinases Liver cancer MAP kinase Molecular modelling Pharmacology Reactive oxygen species ROS Signal transduction Stat3 protein Verification |
| Title | Network pharmacology analysis and experimental verification of the antitumor effect and molecular mechanism of isocryptomerin on HepG2 cells |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fddr.22165 https://www.ncbi.nlm.nih.gov/pubmed/38400652 https://www.proquest.com/docview/3038323749 https://www.proquest.com/docview/2932019257 |
| Volume | 85 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1La9wwEB5CTrn0_XCbFrWU0EO8sWXZssmpNEmXHkIoCeRQMLIeEMLay3r3sP0N_dGdkdbepKVQehOyZFvSjPTZ-uYTwIcqV6pQJouNLEwsrE7j0kkTl6VKhVWyqLRnW5wX0yvx9Tq_3oHjIRYm6EOMP9zIM_x8TQ6umv5oKxpqzGLCeVpQgDlxtQgQfRulowjm-1mYS4oKqtJBVSjhR2PN-2vRHwDzPl71C87ZQ_g-vGrgmdxOVstmon_8puL4n215BA82QJR9CpbzGHZs-wQOLoKS9fqQXW4Ds_pDdsAuthrX66fw8zzQx9n8TjZTG4UTTBh29-wAhg5DnCRvBqxzDGEnFiKawqxbsEAq8bVmw3G9bGYpKPmmn1H5GzSixXq-7GiDCe_Qsqmdf-GM9h36Z3B1dnr5eRpvDnaIdZZmeWyFUk2ZN9zlQpdcV9YgzHOIRLhwQiRGay0S4ZzGhdVpZwql0kynJsEcjnPUc9htu9a-BJZUXEqrjXU5sWFlhWmuZaYyWxmXqwjeD0Ncz4N-Rx2UmnmNvV77Xo9gfxj8euPCfY1rO852mRRVBO_Gy-h81DLV2m7V14iVOGHkXEbwIhjN-JQMP50R3_EIPvqh__vj6xM0XEq8-veir2GPY28FDtE-7C4XK_sG4dGyeev94BcZ7A85 |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB6VcoAL70egBYNQxaHZJo4TJ1IvVaEsUFYV2kq9IMvrh1ShTVab3cPyG_jRjO1NtgUhIW6WYyexPWN_tme-AXhT5VIWUmex5oWOmVFpXFqu47KUKTOSF5Xy1hajYnjOPl3kF1tw2PnCBH6I_sDNaYafr52CuwPpgw1rqNbzAaVpkd-Amy6it99Qfe3JoxzQ9_Mw5c4vqEo7XqGEHvRVr69Gf0DM64jVLzknd-Fb97PB0uT7YLmYDNSP33gc_7c19-DOGouSoyA892HL1A9g7yyQWa_2yXjjm9Xukz1ytqG5Xj2En6NgQU5mV7KJXJOcYEKTq-EDCOqMM0vykkAaSxB5YiFnqTBt5iTYlfha0y5iL5ka55d82U5d-UuUo_lqtmjcHRO-oSZDM_tAibt6aB_B-cn78fEwXsd2iFWWZnlsmJSTMp9QmzNVUlUZjUjPIhihzDKWaKUUS5i1CtdWq6wupEwzleoEcyhOU49hu25q8xRIUlHOjdLG5s4glleYpopnMjOVtrmM4HU3xmIWKDxEIGumAntd-F6PYKcbfbHW4lbg8o4TXsZZFcGr_jHqn2uZrE2zbAXCJepgcs4jeBKkpv9KhrtnhHg0grd-7P_-efEOJdclnv170Zdwazj-cipOP44-P4fbFHsumBTtwPZivjS7iJYWkxdeKX4B7mkTVA |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFD4aQ0K8cGeEbWAQmnhYusRx4kR7QpRSLqoqtEl7QIpcX6QJNYma9qH8hv1oju0m3UBIiDfLsZPYPpcv8TmfAd4UqRCZUEmoeKZCpmUc5oarMM9FzLTgWSFdtMUkG5-zzxfpxQ6cdrkwnh-i_-FmNcPZa6vgjTInW9JQpRYDSuMsvQW3WRblVqSH33ruKIvznRmm3KYFFXFHKxTRk77rTWf0B8K8CVidxxndh-_du_pAkx-D1XI2kD9_o3H8z8E8gHsbJEreedF5CDu6egRHU09lvT4mZ9vMrPaYHJHpluR6_RiuJj5-nDTXqonYUJxgQZHrhwcQ1BgblOTkgNSGIO7ERjZOYV4viI8qcb3m3Xm9ZK5tVvJlO7ftL1GKFutmWdsdJrxDRca6-UiJ3Xhon8D56MPZ-3G4OdkhlEmcpKFmQszydEZNymROZaEV4jyDUIQyw1ikpJQsYsZI9KxGGpUJEScyVhHWUDRST2G3qiv9DEhUUM61VNqkNhyWF1imkici0YUyqQjgdbfEZeMJPEpP1UxLnPXSzXoAB93ilxsdbkt07mjuEs6KAF71l1H77MhEpetVWyJYohYkpzyAPS80_VMS_HZGgEcDeOuW_u-PL4couLbw_N-bvoQ70-Go_Ppp8mUf7lKcOB9PdAC7y8VKHyJUWs5eOJX4BdAtEgw |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Network+pharmacology+analysis+and+experimental+verification+of+the+antitumor+effect+and+molecular+mechanism+of+isocryptomerin+on+HepG2+cells&rft.jtitle=Drug+development+research&rft.au=Cao%2C+Jing-Long&rft.au=Li%2C+Shu-Mei&rft.au=Tang%2C+Yan-Jun&rft.au=Hou%2C+Wen-Shuang&rft.date=2024-04-01&rft.issn=1098-2299&rft.eissn=1098-2299&rft.volume=85&rft.issue=2&rft.spage=e22165&rft_id=info:doi/10.1002%2Fddr.22165&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0272-4391&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0272-4391&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0272-4391&client=summon |