Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells
Abstract Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both ce...
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| Veröffentlicht in: | Cancer letters 2014-03, Vol.344 (2), p.239-259 |
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| container_title | Cancer letters |
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| creator | Li, Yan-Cong He, Shu-Ming He, Zhi-Xu Li, Minghua Yang, Yinxue Pang, Jian-Xin Zhang, Xueji Chow, Kevin Zhou, Qingyu Duan, Wei Zhou, Zhi-Wei Yang, Tianxin Huang, Gui-Hua Liu, Aibing Qiu, Jia-Xuan Liu, Jun-Ping Zhou, Shu-Feng |
| description | Abstract Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways. |
| doi_str_mv | 10.1016/j.canlet.2013.11.001 |
| format | Article |
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This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2013.11.001</identifier><identifier>PMID: 24280585</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Autophagy ; Autophagy - drug effects ; Breast cancer ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Line, Tumor ; Hematology, Oncology and Palliative Medicine ; Humans ; Kinases ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; MAP Kinase Signaling System - drug effects ; Naphthoquinones - pharmacology ; Non-small-cell lung cancer ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; PI3K/Akt/mTOR ; Plumbagin ; Prostate cancer ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Cancer letters, 2014-03, Vol.344 (2), p.239-259</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Mar 28, 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-77903d3d7c5eef0e46842c5b449e5128d3e8160a56883da8354c7617e77f20ff3</citedby><cites>FETCH-LOGICAL-c511t-77903d3d7c5eef0e46842c5b449e5128d3e8160a56883da8354c7617e77f20ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304383513008033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24280585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yan-Cong</creatorcontrib><creatorcontrib>He, Shu-Ming</creatorcontrib><creatorcontrib>He, Zhi-Xu</creatorcontrib><creatorcontrib>Li, Minghua</creatorcontrib><creatorcontrib>Yang, Yinxue</creatorcontrib><creatorcontrib>Pang, Jian-Xin</creatorcontrib><creatorcontrib>Zhang, Xueji</creatorcontrib><creatorcontrib>Chow, Kevin</creatorcontrib><creatorcontrib>Zhou, Qingyu</creatorcontrib><creatorcontrib>Duan, Wei</creatorcontrib><creatorcontrib>Zhou, Zhi-Wei</creatorcontrib><creatorcontrib>Yang, Tianxin</creatorcontrib><creatorcontrib>Huang, Gui-Hua</creatorcontrib><creatorcontrib>Liu, Aibing</creatorcontrib><creatorcontrib>Qiu, Jia-Xuan</creatorcontrib><creatorcontrib>Liu, Jun-Ping</creatorcontrib><creatorcontrib>Zhou, Shu-Feng</creatorcontrib><title>Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Breast cancer</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Line, Tumor</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Naphthoquinones - pharmacology</subject><subject>Non-small-cell lung cancer</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>PI3K/Akt/mTOR</subject><subject>Plumbagin</subject><subject>Prostate cancer</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksFu1DAQhiMEokvhDRCyxIVLdsexHXsvSFVVoKJSKyhny-tMNt4mdogd0D4Fr4y3W0DqhYtHGn3ze2b-KYrXFJYUaL3aLa3xPaZlBZQtKV0C0CfFgipZlXKt4GmxAAa8ZIqJk-JFjDsAEFyK58VJxSsFQolF8eumn4eN2TpPnG9mi5GYMYwpJGeJ8Q0xcwpjlwFLLPY9adCkjqRuCvO2yzWd27jkgiehzVkkN5fs8-rsLq2G2-svZMzwT7PPHOnmwXjigy_jYLLQvVo_-y3Jc1ic7hPxZfGsNX3EVw_xtPj24eL2_FN5df3x8vzsqrSC0lRKuQbWsEZagdgC8lrxyooN52sUtFINQ0VrMKJWijUmr4BbWVOJUrYVtC07Ld4ddccpfJ8xJj24eOjAeAxz1JSvOYMaqMzo20foLsyTz91pKoSsq_zWmeJHyk4hxglbPU5uMNNeU9AHw_ROHw3TB8M0pToblsvePIjPmwGbv0V_HMrA-yOAeRs_HE46Wod5YY2b0CbdBPe_Hx4L2N55Z01_h3uM_2bRsdKgvx6O5nAzlAEoYIz9BrwCvTU</recordid><startdate>20140328</startdate><enddate>20140328</enddate><creator>Li, Yan-Cong</creator><creator>He, Shu-Ming</creator><creator>He, Zhi-Xu</creator><creator>Li, Minghua</creator><creator>Yang, Yinxue</creator><creator>Pang, Jian-Xin</creator><creator>Zhang, Xueji</creator><creator>Chow, Kevin</creator><creator>Zhou, Qingyu</creator><creator>Duan, Wei</creator><creator>Zhou, Zhi-Wei</creator><creator>Yang, Tianxin</creator><creator>Huang, Gui-Hua</creator><creator>Liu, Aibing</creator><creator>Qiu, Jia-Xuan</creator><creator>Liu, Jun-Ping</creator><creator>Zhou, Shu-Feng</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20140328</creationdate><title>Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells</title><author>Li, Yan-Cong ; He, Shu-Ming ; He, Zhi-Xu ; Li, Minghua ; Yang, Yinxue ; Pang, Jian-Xin ; Zhang, Xueji ; Chow, Kevin ; Zhou, Qingyu ; Duan, Wei ; Zhou, Zhi-Wei ; Yang, Tianxin ; Huang, Gui-Hua ; Liu, Aibing ; Qiu, Jia-Xuan ; Liu, Jun-Ping ; Zhou, Shu-Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-77903d3d7c5eef0e46842c5b449e5128d3e8160a56883da8354c7617e77f20ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>Breast cancer</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Line, Tumor</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Naphthoquinones - pharmacology</topic><topic>Non-small-cell lung cancer</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>PI3K/Akt/mTOR</topic><topic>Plumbagin</topic><topic>Prostate cancer</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yan-Cong</creatorcontrib><creatorcontrib>He, Shu-Ming</creatorcontrib><creatorcontrib>He, Zhi-Xu</creatorcontrib><creatorcontrib>Li, Minghua</creatorcontrib><creatorcontrib>Yang, Yinxue</creatorcontrib><creatorcontrib>Pang, Jian-Xin</creatorcontrib><creatorcontrib>Zhang, Xueji</creatorcontrib><creatorcontrib>Chow, Kevin</creatorcontrib><creatorcontrib>Zhou, Qingyu</creatorcontrib><creatorcontrib>Duan, Wei</creatorcontrib><creatorcontrib>Zhou, Zhi-Wei</creatorcontrib><creatorcontrib>Yang, Tianxin</creatorcontrib><creatorcontrib>Huang, Gui-Hua</creatorcontrib><creatorcontrib>Liu, Aibing</creatorcontrib><creatorcontrib>Qiu, Jia-Xuan</creatorcontrib><creatorcontrib>Liu, Jun-Ping</creatorcontrib><creatorcontrib>Zhou, Shu-Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yan-Cong</au><au>He, Shu-Ming</au><au>He, Zhi-Xu</au><au>Li, Minghua</au><au>Yang, Yinxue</au><au>Pang, Jian-Xin</au><au>Zhang, Xueji</au><au>Chow, Kevin</au><au>Zhou, Qingyu</au><au>Duan, Wei</au><au>Zhou, Zhi-Wei</au><au>Yang, Tianxin</au><au>Huang, Gui-Hua</au><au>Liu, Aibing</au><au>Qiu, Jia-Xuan</au><au>Liu, Jun-Ping</au><au>Zhou, Shu-Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2014-03-28</date><risdate>2014</risdate><volume>344</volume><issue>2</issue><spage>239</spage><epage>259</epage><pages>239-259</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>24280585</pmid><doi>10.1016/j.canlet.2013.11.001</doi><tpages>21</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0304-3835 |
| ispartof | Cancer letters, 2014-03, Vol.344 (2), p.239-259 |
| issn | 0304-3835 1872-7980 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Apoptosis Apoptosis - drug effects Autophagy Autophagy - drug effects Breast cancer Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - pathology Cell Line, Tumor Hematology, Oncology and Palliative Medicine Humans Kinases Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - pathology MAP Kinase Signaling System - drug effects Naphthoquinones - pharmacology Non-small-cell lung cancer Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism PI3K/Akt/mTOR Plumbagin Prostate cancer Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism |
| title | Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells |
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