Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells
Tanshinone IIa (TanIIa), an ingredient of Radix Salviae Miltiorrhizae, has an anticancer effect on various solid tumors with high efficiency and low toxicity. Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically i...
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| Veröffentlicht in: | Evidence-based complementary and alternative medicine 2021-10, Vol.2021, p.1-9 |
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| creator | Pan, Yiming Chen, Lingyan Li, Ruibai Liu, Yu Nan, Mengdie Hou, Li |
| description | Tanshinone IIa (TanIIa), an ingredient of Radix Salviae Miltiorrhizae, has an anticancer effect on various solid tumors with high efficiency and low toxicity. Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 μmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells. |
| doi_str_mv | 10.1155/2021/3372403 |
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Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 μmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2021/3372403</identifier><identifier>PMID: 34691211</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>1-Phosphatidylinositol 3-kinase ; Acute promyeloid leukemia ; AKT protein ; Apoptosis ; Autophagy ; Cancer ; Caspase-3 ; Caspase-9 ; Cell cycle ; Cell viability ; Flow cytometry ; Leukemia ; Phagocytosis ; Phosphorylation ; Poly(ADP-ribose) polymerase ; Promyeloid leukemia ; Proteins ; Signal transduction ; Solid tumors ; Tanshinones ; TOR protein ; Toxicity</subject><ispartof>Evidence-based complementary and alternative medicine, 2021-10, Vol.2021, p.1-9</ispartof><rights>Copyright © 2021 Yiming Pan et al.</rights><rights>Copyright © 2021 Yiming Pan 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 Yiming Pan et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-173004fb8ee004aadc8fc097ba88a4b0b8631f5406f958dbcaeb617e929d4ea03</citedby><cites>FETCH-LOGICAL-c425t-173004fb8ee004aadc8fc097ba88a4b0b8631f5406f958dbcaeb617e929d4ea03</cites><orcidid>0000-0003-0172-5559 ; 0000-0003-2921-0821</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/PMC8536410/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536410/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><contributor>Kang, Wen yi</contributor><contributor>Wen yi Kang</contributor><creatorcontrib>Pan, Yiming</creatorcontrib><creatorcontrib>Chen, Lingyan</creatorcontrib><creatorcontrib>Li, Ruibai</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Nan, Mengdie</creatorcontrib><creatorcontrib>Hou, Li</creatorcontrib><title>Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells</title><title>Evidence-based complementary and alternative medicine</title><description>Tanshinone IIa (TanIIa), an ingredient of Radix Salviae Miltiorrhizae, has an anticancer effect on various solid tumors with high efficiency and low toxicity. Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 μmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Acute promyeloid leukemia</subject><subject>AKT protein</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Cancer</subject><subject>Caspase-3</subject><subject>Caspase-9</subject><subject>Cell cycle</subject><subject>Cell viability</subject><subject>Flow cytometry</subject><subject>Leukemia</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Promyeloid leukemia</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Solid tumors</subject><subject>Tanshinones</subject><subject>TOR protein</subject><subject>Toxicity</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>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kU9r3DAQxUVpaNK0t3wAQS6FdLv6Z0u-BNwlTUyWJpQt5CZkeZxVYkuuZafdb19vdwkkh55mmPnNYx4PoRNKvlCaJHNGGJ1zLpkg_A06olLQmWBKvX3u5d0heh_jAyEsk1K-Q4dcpBlllB6hsDI-rp0PHnBRGFz4arQQcT4OoVub-w02vsJ5F7ohRBfxkzP4tuDX8_xxmLermx84_zONnce5HQfAt31oN9AEuxmcxUsYH6GdTr5_FXgBTRM_oIPaNBE-7usx-vntYrW4mi1vLotFvpxZwZJhRiUnRNSlApiqMZVVtSWZLI1SRpSkVCmndSJIWmeJqkproEyphIxllQBD-DE63-l2Y9lCZcEPvWl017vW9BsdjNMvN96t9X140irhqaBbgU97gT78GiEOunXRThaMhzBGzRKVZIxQJif09BX6EMbeT_b-UYykabYV_LyjbB9i7KF-foYSvU1Sb5PU-yQn_GyHT-FU5rf7P_0Xx4OblQ</recordid><startdate>20211015</startdate><enddate>20211015</enddate><creator>Pan, Yiming</creator><creator>Chen, Lingyan</creator><creator>Li, Ruibai</creator><creator>Liu, Yu</creator><creator>Nan, Mengdie</creator><creator>Hou, Li</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</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/0000-0003-0172-5559</orcidid><orcidid>https://orcid.org/0000-0003-2921-0821</orcidid></search><sort><creationdate>20211015</creationdate><title>Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells</title><author>Pan, Yiming ; 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Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 μmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells.</abstract><cop>New York</cop><pub>Hindawi</pub><pmid>34691211</pmid><doi>10.1155/2021/3372403</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0172-5559</orcidid><orcidid>https://orcid.org/0000-0003-2921-0821</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase Acute promyeloid leukemia AKT protein Apoptosis Autophagy Cancer Caspase-3 Caspase-9 Cell cycle Cell viability Flow cytometry Leukemia Phagocytosis Phosphorylation Poly(ADP-ribose) polymerase Promyeloid leukemia Proteins Signal transduction Solid tumors Tanshinones TOR protein Toxicity |
| title | Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells |
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