Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells
Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer eff...
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| Veröffentlicht in: | International journal of biological sciences 2021-01, Vol.17 (13), p.3456-3475 |
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| creator | Zhou, Xuejian Wang, Feifan Wu, Hongshen Chen, Xianwu Zhang, Yan Lin, Juntao Cai, Yueshu Xiang, Jiayong He, Ning Hu, Zhenghui Jin, Xiaodong |
| description | Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells. |
| doi_str_mv | 10.7150/ijbs.60401 |
| format | Article |
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As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.</description><identifier>ISSN: 1449-2288</identifier><identifier>EISSN: 1449-2288</identifier><identifier>DOI: 10.7150/ijbs.60401</identifier><identifier>PMID: 34512159</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>Antibodies ; Anticancer properties ; Apoptosis ; Autophagy ; Autophagy - drug effects ; B7-H1 Antigen - metabolism ; Benzoquinones - pharmacology ; Benzoquinones - therapeutic use ; Biological properties ; Bladder ; Bladder cancer ; Breast cancer ; Carcinoma - drug therapy ; Carcinoma - metabolism ; Caspase ; Cell Line, Tumor ; Cell proliferation ; Clinical outcomes ; Drug Evaluation, Preclinical ; Epithelial-Mesenchymal Transition - drug effects ; Homeostasis ; Humans ; Invasiveness ; Lysosomes ; Medical research ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Mesenchyme ; MicroRNAs ; MicroRNAs - metabolism ; miRNA ; Mitochondria ; PD-L1 protein ; Phagocytosis ; Phagosomes ; Phytochemicals ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Research Paper ; Seeds ; Urinary Bladder Neoplasms - drug therapy ; Urinary Bladder Neoplasms - metabolism</subject><ispartof>International journal of biological sciences, 2021-01, Vol.17 (13), p.3456-3475</ispartof><rights>The author(s).</rights><rights>2021. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-6f587c54d3049928e6e9162bf77e8b99220458f6542ba2e6aef8da7a9b8d3c1d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416733/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416733/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34512159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Xuejian</creatorcontrib><creatorcontrib>Wang, Feifan</creatorcontrib><creatorcontrib>Wu, Hongshen</creatorcontrib><creatorcontrib>Chen, Xianwu</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Lin, Juntao</creatorcontrib><creatorcontrib>Cai, Yueshu</creatorcontrib><creatorcontrib>Xiang, Jiayong</creatorcontrib><creatorcontrib>He, Ning</creatorcontrib><creatorcontrib>Hu, Zhenghui</creatorcontrib><creatorcontrib>Jin, Xiaodong</creatorcontrib><title>Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells</title><title>International journal of biological sciences</title><addtitle>Int J Biol Sci</addtitle><description>Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.</description><subject>Antibodies</subject><subject>Anticancer properties</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Benzoquinones - pharmacology</subject><subject>Benzoquinones - therapeutic use</subject><subject>Biological properties</subject><subject>Bladder</subject><subject>Bladder cancer</subject><subject>Breast cancer</subject><subject>Carcinoma - drug therapy</subject><subject>Carcinoma - metabolism</subject><subject>Caspase</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Clinical outcomes</subject><subject>Drug Evaluation, Preclinical</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Lysosomes</subject><subject>Medical research</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of biological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Xuejian</au><au>Wang, Feifan</au><au>Wu, Hongshen</au><au>Chen, Xianwu</au><au>Zhang, Yan</au><au>Lin, Juntao</au><au>Cai, Yueshu</au><au>Xiang, Jiayong</au><au>He, Ning</au><au>Hu, Zhenghui</au><au>Jin, Xiaodong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells</atitle><jtitle>International journal of biological sciences</jtitle><addtitle>Int J Biol Sci</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>17</volume><issue>13</issue><spage>3456</spage><epage>3475</epage><pages>3456-3475</pages><issn>1449-2288</issn><eissn>1449-2288</eissn><abstract>Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>34512159</pmid><doi>10.7150/ijbs.60401</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Anticancer properties Apoptosis Autophagy Autophagy - drug effects B7-H1 Antigen - metabolism Benzoquinones - pharmacology Benzoquinones - therapeutic use Biological properties Bladder Bladder cancer Breast cancer Carcinoma - drug therapy Carcinoma - metabolism Caspase Cell Line, Tumor Cell proliferation Clinical outcomes Drug Evaluation, Preclinical Epithelial-Mesenchymal Transition - drug effects Homeostasis Humans Invasiveness Lysosomes Medical research Membrane potential Membrane Potential, Mitochondrial - drug effects Mesenchyme MicroRNAs MicroRNAs - metabolism miRNA Mitochondria PD-L1 protein Phagocytosis Phagosomes Phytochemicals Reactive oxygen species Reactive Oxygen Species - metabolism Research Paper Seeds Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - metabolism |
| title | Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells |
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