Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome
Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective n...
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| Veröffentlicht in: | Journal of natural products (Washington, D.C.) D.C.), 2024-06, Vol.87 (6), p.1501-1512 |
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| creator | Cao, Danli Lin, Yiru Lin, Caiji Xu, Mengzhi Wang, Jiaxing Zeng, Zheng Wang, Pengfei Li, Qinghai Wang, Xiaoyu Wang, Wenxue Luo, Lingjie Zhao, Yufan Shi, Yongwei Gao, Zixiang Kang, Xin Wang, Shuang Zhang, Yuanyuan Xu, Xiaohui Liu, Shu-Lin Liu, Huidi |
| description | Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway. |
| doi_str_mv | 10.1021/acs.jnatprod.3c00782 |
| format | Article |
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Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.</description><identifier>ISSN: 0163-3864</identifier><identifier>ISSN: 1520-6025</identifier><identifier>EISSN: 1520-6025</identifier><identifier>DOI: 10.1021/acs.jnatprod.3c00782</identifier><identifier>PMID: 38603577</identifier><language>eng</language><publisher>United States: American Chemical Society and American Society of Pharmacognosy</publisher><subject>adjuvants ; apoptosis ; cannabidiol ; cytotoxicity ; dose response ; drug development ; drug resistance ; epithelium ; intestinal microorganisms ; ovarian neoplasms ; surgery ; tetrahydrocannabinol ; Western blotting</subject><ispartof>Journal of natural products (Washington, D.C.), 2024-06, Vol.87 (6), p.1501-1512</ispartof><rights>2024 American Chemical Society and American Society of Pharmacognosy</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a330t-bf457cdee5dcd28d30a3845f9200855417c63696f61196756091c7e9a09494053</cites><orcidid>0000-0002-9859-3013</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.3c00782$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jnatprod.3c00782$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,777,781,2752,27057,27905,27906,56719,56769</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38603577$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Danli</creatorcontrib><creatorcontrib>Lin, Yiru</creatorcontrib><creatorcontrib>Lin, Caiji</creatorcontrib><creatorcontrib>Xu, Mengzhi</creatorcontrib><creatorcontrib>Wang, Jiaxing</creatorcontrib><creatorcontrib>Zeng, Zheng</creatorcontrib><creatorcontrib>Wang, Pengfei</creatorcontrib><creatorcontrib>Li, Qinghai</creatorcontrib><creatorcontrib>Wang, Xiaoyu</creatorcontrib><creatorcontrib>Wang, Wenxue</creatorcontrib><creatorcontrib>Luo, Lingjie</creatorcontrib><creatorcontrib>Zhao, Yufan</creatorcontrib><creatorcontrib>Shi, Yongwei</creatorcontrib><creatorcontrib>Gao, Zixiang</creatorcontrib><creatorcontrib>Kang, Xin</creatorcontrib><creatorcontrib>Wang, Shuang</creatorcontrib><creatorcontrib>Zhang, Yuanyuan</creatorcontrib><creatorcontrib>Xu, Xiaohui</creatorcontrib><creatorcontrib>Liu, Shu-Lin</creatorcontrib><creatorcontrib>Liu, Huidi</creatorcontrib><title>Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome</title><title>Journal of natural products (Washington, D.C.)</title><addtitle>J. Nat. Prod</addtitle><description>Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.</description><subject>adjuvants</subject><subject>apoptosis</subject><subject>cannabidiol</subject><subject>cytotoxicity</subject><subject>dose response</subject><subject>drug development</subject><subject>drug resistance</subject><subject>epithelium</subject><subject>intestinal microorganisms</subject><subject>ovarian neoplasms</subject><subject>surgery</subject><subject>tetrahydrocannabinol</subject><subject>Western blotting</subject><issn>0163-3864</issn><issn>1520-6025</issn><issn>1520-6025</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkE1LAzEQhoMotlb_gUiOXrZONh-78SalrQWlIHoO2WyWpuxHTXYF_73Rth71NDA87zvMg9A1gSmBlNxpE6bbVvc735VTagCyPD1BY8JTSASk_BSNgQia0FywEboIYQsAFCQ_R6O4A8qzbIwWM922unCl62q8ajeucH3A853rN7Z2usbrD-2dbnHkjPX3-KWrLe4qvBx6_OyM7wrXNfYSnVW6DvbqMCfobTF_nT0mT-vlavbwlGhKoU-KivHMlNby0pRpXlLQNGe8kilAzjkjmRFUSFEJQqTIuABJTGalBskkA04n6HbfG79-H2zoVeOCsXWtW9sNQVHCqcgk4fA_CvE0Y5ynEWV7NL4TgreV2nnXaP-pCKhv2SrKVkfZ6iA7xm4OF4aiseVv6Gg3ArAHfuLd4Nvo5u_OL51fjBU</recordid><startdate>20240628</startdate><enddate>20240628</enddate><creator>Cao, Danli</creator><creator>Lin, Yiru</creator><creator>Lin, Caiji</creator><creator>Xu, Mengzhi</creator><creator>Wang, Jiaxing</creator><creator>Zeng, Zheng</creator><creator>Wang, Pengfei</creator><creator>Li, Qinghai</creator><creator>Wang, Xiaoyu</creator><creator>Wang, Wenxue</creator><creator>Luo, Lingjie</creator><creator>Zhao, Yufan</creator><creator>Shi, Yongwei</creator><creator>Gao, Zixiang</creator><creator>Kang, Xin</creator><creator>Wang, Shuang</creator><creator>Zhang, Yuanyuan</creator><creator>Xu, Xiaohui</creator><creator>Liu, Shu-Lin</creator><creator>Liu, Huidi</creator><general>American Chemical Society and American Society of Pharmacognosy</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-9859-3013</orcidid></search><sort><creationdate>20240628</creationdate><title>Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome</title><author>Cao, Danli ; Lin, Yiru ; Lin, Caiji ; Xu, Mengzhi ; Wang, Jiaxing ; Zeng, Zheng ; Wang, Pengfei ; Li, Qinghai ; Wang, Xiaoyu ; Wang, Wenxue ; Luo, Lingjie ; Zhao, Yufan ; Shi, Yongwei ; Gao, Zixiang ; Kang, Xin ; Wang, Shuang ; Zhang, Yuanyuan ; Xu, Xiaohui ; Liu, Shu-Lin ; Liu, Huidi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a330t-bf457cdee5dcd28d30a3845f9200855417c63696f61196756091c7e9a09494053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>adjuvants</topic><topic>apoptosis</topic><topic>cannabidiol</topic><topic>cytotoxicity</topic><topic>dose response</topic><topic>drug development</topic><topic>drug resistance</topic><topic>epithelium</topic><topic>intestinal microorganisms</topic><topic>ovarian neoplasms</topic><topic>surgery</topic><topic>tetrahydrocannabinol</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Danli</creatorcontrib><creatorcontrib>Lin, Yiru</creatorcontrib><creatorcontrib>Lin, Caiji</creatorcontrib><creatorcontrib>Xu, Mengzhi</creatorcontrib><creatorcontrib>Wang, Jiaxing</creatorcontrib><creatorcontrib>Zeng, Zheng</creatorcontrib><creatorcontrib>Wang, Pengfei</creatorcontrib><creatorcontrib>Li, Qinghai</creatorcontrib><creatorcontrib>Wang, Xiaoyu</creatorcontrib><creatorcontrib>Wang, Wenxue</creatorcontrib><creatorcontrib>Luo, Lingjie</creatorcontrib><creatorcontrib>Zhao, Yufan</creatorcontrib><creatorcontrib>Shi, Yongwei</creatorcontrib><creatorcontrib>Gao, Zixiang</creatorcontrib><creatorcontrib>Kang, Xin</creatorcontrib><creatorcontrib>Wang, Shuang</creatorcontrib><creatorcontrib>Zhang, Yuanyuan</creatorcontrib><creatorcontrib>Xu, Xiaohui</creatorcontrib><creatorcontrib>Liu, Shu-Lin</creatorcontrib><creatorcontrib>Liu, Huidi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Journal of natural products (Washington, D.C.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Danli</au><au>Lin, Yiru</au><au>Lin, Caiji</au><au>Xu, Mengzhi</au><au>Wang, Jiaxing</au><au>Zeng, Zheng</au><au>Wang, Pengfei</au><au>Li, Qinghai</au><au>Wang, Xiaoyu</au><au>Wang, Wenxue</au><au>Luo, Lingjie</au><au>Zhao, Yufan</au><au>Shi, Yongwei</au><au>Gao, Zixiang</au><au>Kang, Xin</au><au>Wang, Shuang</au><au>Zhang, Yuanyuan</au><au>Xu, Xiaohui</au><au>Liu, Shu-Lin</au><au>Liu, Huidi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome</atitle><jtitle>Journal of natural products (Washington, D.C.)</jtitle><addtitle>J. Nat. Prod</addtitle><date>2024-06-28</date><risdate>2024</risdate><volume>87</volume><issue>6</issue><spage>1501</spage><epage>1512</epage><pages>1501-1512</pages><issn>0163-3864</issn><issn>1520-6025</issn><eissn>1520-6025</eissn><abstract>Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.</abstract><cop>United States</cop><pub>American Chemical Society and American Society of Pharmacognosy</pub><pmid>38603577</pmid><doi>10.1021/acs.jnatprod.3c00782</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9859-3013</orcidid></addata></record> |
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| source | ACS Publications |
| subjects | adjuvants apoptosis cannabidiol cytotoxicity dose response drug development drug resistance epithelium intestinal microorganisms ovarian neoplasms surgery tetrahydrocannabinol Western blotting |
| title | Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome |
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