Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways
The extract of Broussonetia papyrifera has been proved to have antitumor activity. However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inh...
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| Veröffentlicht in: | Evidence-based complementary and alternative medicine 2021, Vol.2021, p.8841706-11 |
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| creator | Dou, Chen-Zhuo Liu, Yan-Fen Zhang, Lu-Lu Chen, Shao-Hong Hu, Chuan-Yin Liu, You Zhao, Yun-Tao |
| description | The extract of Broussonetia papyrifera has been proved to have antitumor activity. However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways. |
| doi_str_mv | 10.1155/2021/8841706 |
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However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2021/8841706</identifier><identifier>PMID: 33884026</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>AKT protein ; Antitumor activity ; Apoptosis ; BAX protein ; Bcl-2 protein ; Broussonetia papyrifera ; Cancer ; Caspase-3 ; Cell cycle ; Cell proliferation ; Ethanol ; Extracellular signal-regulated kinase ; Flow cytometry ; G1 phase ; Intracellular ; Medical prognosis ; Medical research ; Mitochondria ; p53 Protein ; Phytochemicals ; Polyphenols ; Reactive oxygen species ; Signal transduction ; Superoxide dismutase ; Western blotting</subject><ispartof>Evidence-based complementary and alternative medicine, 2021, Vol.2021, p.8841706-11</ispartof><rights>Copyright © 2021 Chen-Zhuo Dou et al.</rights><rights>Copyright © 2021 Chen-Zhuo Dou et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Chen-Zhuo Dou et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-952eca9554332ec624235ae089a36ba65b0cfab8127836cf1eb4b123bc37d8903</citedby><cites>FETCH-LOGICAL-c448t-952eca9554332ec624235ae089a36ba65b0cfab8127836cf1eb4b123bc37d8903</cites><orcidid>0000-0003-0378-2880 ; 0000-0003-1122-6139 ; 0000-0002-1049-6113</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009708/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009708/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33884026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ferraro, Maria</contributor><contributor>Maria Ferraro</contributor><creatorcontrib>Dou, Chen-Zhuo</creatorcontrib><creatorcontrib>Liu, Yan-Fen</creatorcontrib><creatorcontrib>Zhang, Lu-Lu</creatorcontrib><creatorcontrib>Chen, Shao-Hong</creatorcontrib><creatorcontrib>Hu, Chuan-Yin</creatorcontrib><creatorcontrib>Liu, You</creatorcontrib><creatorcontrib>Zhao, Yun-Tao</creatorcontrib><title>Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>The extract of Broussonetia papyrifera has been proved to have antitumor activity. However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways.</description><subject>AKT protein</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Broussonetia papyrifera</subject><subject>Cancer</subject><subject>Caspase-3</subject><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Ethanol</subject><subject>Extracellular signal-regulated kinase</subject><subject>Flow cytometry</subject><subject>G1 phase</subject><subject>Intracellular</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Mitochondria</subject><subject>p53 Protein</subject><subject>Phytochemicals</subject><subject>Polyphenols</subject><subject>Reactive oxygen species</subject><subject>Signal transduction</subject><subject>Superoxide dismutase</subject><subject>Western blotting</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kd9rFDEQx4MotlbffJaAL4KezY_NJvsinEdtSwsWreBbmM1m71L2kjXZvXL0n2-WOw_1wacZmM98me98EXpNyUdKhThlhNFTpQoqSfkEHVNZ0FnBlHp66OXPI_QipTtCWCWlfI6OOM8LhJXH6OEmdNt-ZX3oEm5jWOPPMYwpBW8HB7iHfhtdayPgS9-MxuJ5H_ohJJdwaPGF7c8ZXtguL2_cxIAZ3AYGF_w0P_t2hcE3eH51i7-7pYfO-SW-gWF1D9v0Ej1roUv21b6eoB9fzm4XF7Prr-eXi_n1zBSFGmaVYNZAJUTBee5KVjAuwBJVAS9rKEVNTAu1okwqXpqW2rqoKeO14bJRFeEn6NNOtx_rtW2M9UOETvfRrSFudQCn_554t9LLsNGKkEoSlQXe7QVi-DXaNOi1Sya7Bm_zszQTtMwBMFlk9O0_6F0YYzY-UUQxKQWjmfqwo0wMKUXbHo6hRE-p6ilVvU8142_-NHCAf8eYgfc7YOV8A_fu_3KPYPOqkg</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Dou, Chen-Zhuo</creator><creator>Liu, Yan-Fen</creator><creator>Zhang, Lu-Lu</creator><creator>Chen, Shao-Hong</creator><creator>Hu, Chuan-Yin</creator><creator>Liu, You</creator><creator>Zhao, Yun-Tao</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0378-2880</orcidid><orcidid>https://orcid.org/0000-0003-1122-6139</orcidid><orcidid>https://orcid.org/0000-0002-1049-6113</orcidid></search><sort><creationdate>2021</creationdate><title>Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways</title><author>Dou, Chen-Zhuo ; 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However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>33884026</pmid><doi>10.1155/2021/8841706</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0378-2880</orcidid><orcidid>https://orcid.org/0000-0003-1122-6139</orcidid><orcidid>https://orcid.org/0000-0002-1049-6113</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | AKT protein Antitumor activity Apoptosis BAX protein Bcl-2 protein Broussonetia papyrifera Cancer Caspase-3 Cell cycle Cell proliferation Ethanol Extracellular signal-regulated kinase Flow cytometry G1 phase Intracellular Medical prognosis Medical research Mitochondria p53 Protein Phytochemicals Polyphenols Reactive oxygen species Signal transduction Superoxide dismutase Western blotting |
| title | Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways |
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