Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer
Cannabidiol, a major non-psychotomimetic compound derived from , is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TR...
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| Veröffentlicht in: | Cancers 2019-05, Vol.11 (5), p.642 |
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| creator | Kim, Jung Lim Kim, Bo Ram Kim, Dae Yeong Jeong, Yoon A Jeong, Soyeon Na, Yoo Jin Park, Seong Hye Yun, Hye Kyeong Jo, Min Jee Kim, Bu Gyeom Kim, Han Do Kim, Dae Hyun Oh, Sang Cheul Lee, Sun Il Lee, Dae-Hee |
| description | Cannabidiol, a major non-psychotomimetic compound derived from
, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol. Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidiol and TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models. Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL. |
| doi_str_mv | 10.3390/cancers11050642 |
| format | Article |
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, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol. Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidiol and TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models. Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers11050642</identifier><identifier>PMID: 31075907</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibodies ; Antitumor activity ; Apoptosis ; Brain cancer ; Cancer therapies ; Cannabidiol ; Cannabinoids ; Cannabis ; CCAAT/enhancer-binding protein ; Colorectal cancer ; Colorectal carcinoma ; Flow cytometry ; Inflammatory diseases ; Microscopy ; Neurodegenerative diseases ; Protein kinase ; Proteins ; Radiation ; Reagents ; TRAIL protein ; Tumor necrosis factor ; Xenografts</subject><ispartof>Cancers, 2019-05, Vol.11 (5), p.642</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-c3331c978605997a6b59106f0b756446c2a789fafcf55ffe24060814687be5d3</citedby><cites>FETCH-LOGICAL-c421t-c3331c978605997a6b59106f0b756446c2a789fafcf55ffe24060814687be5d3</cites><orcidid>0000-0002-3793-7847</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/PMC6562873/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562873/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31075907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jung Lim</creatorcontrib><creatorcontrib>Kim, Bo Ram</creatorcontrib><creatorcontrib>Kim, Dae Yeong</creatorcontrib><creatorcontrib>Jeong, Yoon A</creatorcontrib><creatorcontrib>Jeong, Soyeon</creatorcontrib><creatorcontrib>Na, Yoo Jin</creatorcontrib><creatorcontrib>Park, Seong Hye</creatorcontrib><creatorcontrib>Yun, Hye Kyeong</creatorcontrib><creatorcontrib>Jo, Min Jee</creatorcontrib><creatorcontrib>Kim, Bu Gyeom</creatorcontrib><creatorcontrib>Kim, Han Do</creatorcontrib><creatorcontrib>Kim, Dae Hyun</creatorcontrib><creatorcontrib>Oh, Sang Cheul</creatorcontrib><creatorcontrib>Lee, Sun Il</creatorcontrib><creatorcontrib>Lee, Dae-Hee</creatorcontrib><title>Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Cannabidiol, a major non-psychotomimetic compound derived from
, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol. Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidiol and TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models. Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL.</description><subject>Antibodies</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Brain cancer</subject><subject>Cancer therapies</subject><subject>Cannabidiol</subject><subject>Cannabinoids</subject><subject>Cannabis</subject><subject>CCAAT/enhancer-binding protein</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Flow cytometry</subject><subject>Inflammatory diseases</subject><subject>Microscopy</subject><subject>Neurodegenerative diseases</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Radiation</subject><subject>Reagents</subject><subject>TRAIL protein</subject><subject>Tumor necrosis factor</subject><subject>Xenografts</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1LKzEYhYMoKuranQTcuOk135lsBBnrVSgIUreGTJq0kWlSkxnBf2-8ekV9N3khTw7n5ABwjNEfShU6tyZalwvGiCPByBbYJ0iSiRCKbX_b98BRKU-oDqVYCrkL9ihGkisk98Fja2I0XViE1MNpXL1LFjisHJyvXDYbNw7Bwqn3zg4FJg_n95e3M9i9wodNdsuxN0OIS3h1z2GIsE19ypU0PWz_mTsEO970xR19ngdgfj2dtzeT2d3f2_ZyNrGM4GFiabVmlWwE4kpJIzquMBIedZILxoQlRjbKG28959ULYUigBjPRyM7xBT0AFx-ym7Fbu4V1ccim15sc1ia_6mSC_nkTw0ov04sWXJBG0ipw9imQ0_PoyqDXoVjX9ya6NBZNCMUKCSJJRU9_oU9pzLGm04Qzyeq3NrhS5x-UzamU7PyXGYz0e3v6V3v1xcn3DF_8_67oG3TLlZs</recordid><startdate>20190509</startdate><enddate>20190509</enddate><creator>Kim, Jung Lim</creator><creator>Kim, Bo Ram</creator><creator>Kim, Dae Yeong</creator><creator>Jeong, Yoon A</creator><creator>Jeong, Soyeon</creator><creator>Na, Yoo Jin</creator><creator>Park, Seong Hye</creator><creator>Yun, Hye Kyeong</creator><creator>Jo, Min Jee</creator><creator>Kim, Bu Gyeom</creator><creator>Kim, Han Do</creator><creator>Kim, Dae Hyun</creator><creator>Oh, Sang Cheul</creator><creator>Lee, Sun Il</creator><creator>Lee, Dae-Hee</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3793-7847</orcidid></search><sort><creationdate>20190509</creationdate><title>Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer</title><author>Kim, Jung Lim ; Kim, Bo Ram ; Kim, Dae Yeong ; Jeong, Yoon A ; Jeong, Soyeon ; Na, Yoo Jin ; Park, Seong Hye ; Yun, Hye Kyeong ; Jo, Min Jee ; Kim, Bu Gyeom ; Kim, Han Do ; Kim, Dae Hyun ; Oh, Sang Cheul ; Lee, Sun Il ; Lee, Dae-Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-c3331c978605997a6b59106f0b756446c2a789fafcf55ffe24060814687be5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antibodies</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Brain cancer</topic><topic>Cancer therapies</topic><topic>Cannabidiol</topic><topic>Cannabinoids</topic><topic>Cannabis</topic><topic>CCAAT/enhancer-binding protein</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Flow cytometry</topic><topic>Inflammatory diseases</topic><topic>Microscopy</topic><topic>Neurodegenerative diseases</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Radiation</topic><topic>Reagents</topic><topic>TRAIL protein</topic><topic>Tumor necrosis factor</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jung Lim</creatorcontrib><creatorcontrib>Kim, Bo Ram</creatorcontrib><creatorcontrib>Kim, Dae Yeong</creatorcontrib><creatorcontrib>Jeong, Yoon A</creatorcontrib><creatorcontrib>Jeong, Soyeon</creatorcontrib><creatorcontrib>Na, Yoo Jin</creatorcontrib><creatorcontrib>Park, Seong Hye</creatorcontrib><creatorcontrib>Yun, Hye Kyeong</creatorcontrib><creatorcontrib>Jo, Min Jee</creatorcontrib><creatorcontrib>Kim, Bu Gyeom</creatorcontrib><creatorcontrib>Kim, Han Do</creatorcontrib><creatorcontrib>Kim, Dae Hyun</creatorcontrib><creatorcontrib>Oh, Sang Cheul</creatorcontrib><creatorcontrib>Lee, Sun Il</creatorcontrib><creatorcontrib>Lee, Dae-Hee</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jung Lim</au><au>Kim, Bo Ram</au><au>Kim, Dae Yeong</au><au>Jeong, Yoon A</au><au>Jeong, Soyeon</au><au>Na, Yoo Jin</au><au>Park, Seong Hye</au><au>Yun, Hye Kyeong</au><au>Jo, Min Jee</au><au>Kim, Bu Gyeom</au><au>Kim, Han Do</au><au>Kim, Dae Hyun</au><au>Oh, Sang Cheul</au><au>Lee, Sun Il</au><au>Lee, Dae-Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2019-05-09</date><risdate>2019</risdate><volume>11</volume><issue>5</issue><spage>642</spage><pages>642-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Cannabidiol, a major non-psychotomimetic compound derived from
, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol. Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidiol and TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models. Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31075907</pmid><doi>10.3390/cancers11050642</doi><orcidid>https://orcid.org/0000-0002-3793-7847</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Antitumor activity Apoptosis Brain cancer Cancer therapies Cannabidiol Cannabinoids Cannabis CCAAT/enhancer-binding protein Colorectal cancer Colorectal carcinoma Flow cytometry Inflammatory diseases Microscopy Neurodegenerative diseases Protein kinase Proteins Radiation Reagents TRAIL protein Tumor necrosis factor Xenografts |
| title | Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer |
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