Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer
•3D spheroids are more resistant to Hypericin-PDT than 2D cell models.•ABCG2 is upregulated in 3D spheroids as compared to 2D cell models.•Inhibiting ABCG2 could potentially improve response to Hypericin-PDT. Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study...
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| Veröffentlicht in: | Photodiagnosis and photodynamic therapy 2018-09, Vol.23, p.221-229 |
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| container_title | Photodiagnosis and photodynamic therapy |
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| creator | Khot, M. Ibrahim Perry, Sarah L. Maisey, Thomas Armstrong, Gemma Andrew, Helen Hughes, Thomas A. Kapur, Nikil Jayne, David G. |
| description | •3D spheroids are more resistant to Hypericin-PDT than 2D cell models.•ABCG2 is upregulated in 3D spheroids as compared to 2D cell models.•Inhibiting ABCG2 could potentially improve response to Hypericin-PDT.
Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids.
Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm2) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated.
Hypericin-PDT produced a significant reduction in HT29 (p |
| doi_str_mv | 10.1016/j.pdpdt.2018.06.027 |
| format | Article |
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Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids.
Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm2) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated.
Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01).
Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition.</description><identifier>ISSN: 1572-1000</identifier><identifier>EISSN: 1873-1597</identifier><identifier>DOI: 10.1016/j.pdpdt.2018.06.027</identifier><identifier>PMID: 29969677</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>ABCG2 ; Apoptosis - drug effects ; ATP Binding Cassette Transporter, Subfamily G, Member 2 - antagonists & inhibitors ; Cell Survival - drug effects ; Colorectal cancer ; Colorectal Neoplasms - drug therapy ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; HCT116 Cells ; HT29 Cells ; Humans ; Hypericin ; Ko143 ; Multicellular tumour spheroids ; Perylene - administration & dosage ; Perylene - analogs & derivatives ; Perylene - pharmacology ; Photochemotherapy - methods ; Photodynamic therapy ; Photosensitizing Agents - administration & dosage ; Photosensitizing Agents - pharmacology ; Spheroids, Cellular</subject><ispartof>Photodiagnosis and photodynamic therapy, 2018-09, Vol.23, p.221-229</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-2461709ff53e3a2fa455ddc30879c45ffda0d177d9fa6978050c5e124e3207cf3</citedby><cites>FETCH-LOGICAL-c404t-2461709ff53e3a2fa455ddc30879c45ffda0d177d9fa6978050c5e124e3207cf3</cites><orcidid>0000-0003-1555-7699 ; 0000-0003-1169-3386 ; 0000-0002-2561-8195</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.pdpdt.2018.06.027$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29969677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khot, M. Ibrahim</creatorcontrib><creatorcontrib>Perry, Sarah L.</creatorcontrib><creatorcontrib>Maisey, Thomas</creatorcontrib><creatorcontrib>Armstrong, Gemma</creatorcontrib><creatorcontrib>Andrew, Helen</creatorcontrib><creatorcontrib>Hughes, Thomas A.</creatorcontrib><creatorcontrib>Kapur, Nikil</creatorcontrib><creatorcontrib>Jayne, David G.</creatorcontrib><title>Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer</title><title>Photodiagnosis and photodynamic therapy</title><addtitle>Photodiagnosis Photodyn Ther</addtitle><description>•3D spheroids are more resistant to Hypericin-PDT than 2D cell models.•ABCG2 is upregulated in 3D spheroids as compared to 2D cell models.•Inhibiting ABCG2 could potentially improve response to Hypericin-PDT.
Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids.
Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm2) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated.
Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01).
Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition.</description><subject>ABCG2</subject><subject>Apoptosis - drug effects</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 2 - antagonists & inhibitors</subject><subject>Cell Survival - drug effects</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Delivery Systems</subject><subject>HCT116 Cells</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Hypericin</subject><subject>Ko143</subject><subject>Multicellular tumour spheroids</subject><subject>Perylene - administration & dosage</subject><subject>Perylene - analogs & derivatives</subject><subject>Perylene - pharmacology</subject><subject>Photochemotherapy - methods</subject><subject>Photodynamic therapy</subject><subject>Photosensitizing Agents - administration & dosage</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Spheroids, Cellular</subject><issn>1572-1000</issn><issn>1873-1597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1TAQRSMEoqXwBUjISzYJY8eJ4wWL8gRtpUpsYG259pj4KYmD7YeUz-CPcXiFZVceyffOHZ1bVW8pNBRo_-HYrHa1uWFAhwb6Bph4Vl3SQbQ17aR4XuZOsJoCwEX1KqUjQMsl8JfVBZOyl70Ql9Xvu2X0Dz775Qe5_nS4YcSE02TJGjIu2etp2gguo14MkjwiQee80WYjwZFxWzF645d6Rut1xmIbQw52W_Tsza6Pet2IX0hayxy81RMxOE1kDhantC8xYQoRTd5_9pT4unrh9JTwzeN7VX3_8vnb4ba-_3pzd7i-rw0HnmvGeypAOte12GrmNO86a00Lg5CGd85ZDZYKYaXTvRQDdGA6pIxjy0AY115V78971xh-njBlNfu0H6cXDKekGPSccTZQWaTtWWpiSCmiU2v0s46boqD2LtRR_e1C7V0o6FXporjePQacHgqg_55_8Ivg41lQUOAvj1El47EwsH4nomzwTwb8AWXLnnc</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Khot, M. Ibrahim</creator><creator>Perry, Sarah L.</creator><creator>Maisey, Thomas</creator><creator>Armstrong, Gemma</creator><creator>Andrew, Helen</creator><creator>Hughes, Thomas A.</creator><creator>Kapur, Nikil</creator><creator>Jayne, David G.</creator><general>Elsevier B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0003-1555-7699</orcidid><orcidid>https://orcid.org/0000-0003-1169-3386</orcidid><orcidid>https://orcid.org/0000-0002-2561-8195</orcidid></search><sort><creationdate>201809</creationdate><title>Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer</title><author>Khot, M. Ibrahim ; Perry, Sarah L. ; Maisey, Thomas ; Armstrong, Gemma ; Andrew, Helen ; Hughes, Thomas A. ; Kapur, Nikil ; Jayne, David G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-2461709ff53e3a2fa455ddc30879c45ffda0d177d9fa6978050c5e124e3207cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>ABCG2</topic><topic>Apoptosis - drug effects</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 2 - antagonists & inhibitors</topic><topic>Cell Survival - drug effects</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Delivery Systems</topic><topic>HCT116 Cells</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Hypericin</topic><topic>Ko143</topic><topic>Multicellular tumour spheroids</topic><topic>Perylene - administration & dosage</topic><topic>Perylene - analogs & derivatives</topic><topic>Perylene - pharmacology</topic><topic>Photochemotherapy - methods</topic><topic>Photodynamic therapy</topic><topic>Photosensitizing Agents - administration & dosage</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Spheroids, Cellular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khot, M. Ibrahim</creatorcontrib><creatorcontrib>Perry, Sarah L.</creatorcontrib><creatorcontrib>Maisey, Thomas</creatorcontrib><creatorcontrib>Armstrong, Gemma</creatorcontrib><creatorcontrib>Andrew, Helen</creatorcontrib><creatorcontrib>Hughes, Thomas A.</creatorcontrib><creatorcontrib>Kapur, Nikil</creatorcontrib><creatorcontrib>Jayne, David G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Photodiagnosis and photodynamic therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khot, M. Ibrahim</au><au>Perry, Sarah L.</au><au>Maisey, Thomas</au><au>Armstrong, Gemma</au><au>Andrew, Helen</au><au>Hughes, Thomas A.</au><au>Kapur, Nikil</au><au>Jayne, David G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer</atitle><jtitle>Photodiagnosis and photodynamic therapy</jtitle><addtitle>Photodiagnosis Photodyn Ther</addtitle><date>2018-09</date><risdate>2018</risdate><volume>23</volume><spage>221</spage><epage>229</epage><pages>221-229</pages><issn>1572-1000</issn><eissn>1873-1597</eissn><abstract>•3D spheroids are more resistant to Hypericin-PDT than 2D cell models.•ABCG2 is upregulated in 3D spheroids as compared to 2D cell models.•Inhibiting ABCG2 could potentially improve response to Hypericin-PDT.
Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids.
Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm2) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated.
Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01).
Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>29969677</pmid><doi>10.1016/j.pdpdt.2018.06.027</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1555-7699</orcidid><orcidid>https://orcid.org/0000-0003-1169-3386</orcidid><orcidid>https://orcid.org/0000-0002-2561-8195</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | ABCG2 Apoptosis - drug effects ATP Binding Cassette Transporter, Subfamily G, Member 2 - antagonists & inhibitors Cell Survival - drug effects Colorectal cancer Colorectal Neoplasms - drug therapy Dose-Response Relationship, Drug Drug Delivery Systems HCT116 Cells HT29 Cells Humans Hypericin Ko143 Multicellular tumour spheroids Perylene - administration & dosage Perylene - analogs & derivatives Perylene - pharmacology Photochemotherapy - methods Photodynamic therapy Photosensitizing Agents - administration & dosage Photosensitizing Agents - pharmacology Spheroids, Cellular |
| title | Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer |
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