Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway
A study on the secondary metabolites of <i>Aspergillus sp</i>. XNM-4, which was derived from marine algae <i>Leathesia nana</i> (Chordariaceae), led to the identification of one previously undescribed (<b>1</b>) and seventeen known compounds (<b>2</b>&...
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MDPI AG
2019-04-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/17/4/207 |
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| author | Kuo Xu Chuanlong Guo Jie Meng Haiying Tian Shuju Guo Dayong Shi |
| author_facet | Kuo Xu Chuanlong Guo Jie Meng Haiying Tian Shuju Guo Dayong Shi |
| author_sort | Kuo Xu |
| collection | DOAJ |
| description | A study on the secondary metabolites of <i>Aspergillus sp</i>. XNM-4, which was derived from marine algae <i>Leathesia nana</i> (Chordariaceae), led to the identification of one previously undescribed (<b>1</b>) and seventeen known compounds (<b>2</b>–<b>18</b>). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones <b>7</b>, <b>10</b> and <b>12</b> exhibited potent cytotoxicity. Further mechanism studies showed that <b>12</b> induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway. |
| first_indexed | 2024-04-13T08:09:22Z |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T08:09:22Z |
| publishDate | 2019-04-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-c3b75c41c54e4b75807bf2fb98307b212022-12-22T02:55:04ZengMDPI AGMarine Drugs1660-33972019-04-0117420710.3390/md17040207md17040207Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic PathwayKuo Xu0Chuanlong Guo1Jie Meng2Haiying Tian3Shuju Guo4Dayong Shi5Chinese Academy of Sciences Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaChinese Academy of Sciences Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaChinese Academy of Sciences Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaTechnology Center, China Tobacco Henan Industrial Co., Ltd., Zhengzhou, 450000, ChinaChinese Academy of Sciences Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaChinese Academy of Sciences Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaA study on the secondary metabolites of <i>Aspergillus sp</i>. XNM-4, which was derived from marine algae <i>Leathesia nana</i> (Chordariaceae), led to the identification of one previously undescribed (<b>1</b>) and seventeen known compounds (<b>2</b>–<b>18</b>). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones <b>7</b>, <b>10</b> and <b>12</b> exhibited potent cytotoxicity. Further mechanism studies showed that <b>12</b> induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.https://www.mdpi.com/1660-3397/17/4/207<i>Aspergillus</i>naphthopyronescytotoxicityendophytic fungus<i>Leathesia nana</i> |
| spellingShingle | Kuo Xu Chuanlong Guo Jie Meng Haiying Tian Shuju Guo Dayong Shi Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway Marine Drugs <i>Aspergillus</i> naphthopyrones cytotoxicity endophytic fungus <i>Leathesia nana</i> |
| title | Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway |
| title_full | Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway |
| title_fullStr | Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway |
| title_full_unstemmed | Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway |
| title_short | Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway |
| title_sort | discovery of natural dimeric naphthopyrones as potential cytotoxic agents through ros mediated apoptotic pathway |
| topic | <i>Aspergillus</i> naphthopyrones cytotoxicity endophytic fungus <i>Leathesia nana</i> |
| url | https://www.mdpi.com/1660-3397/17/4/207 |
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