Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells
Although the anticancer activity of Dorstenia foetida was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, i.e., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (1) and 5-methoxy-3-(3...
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Sciendo
2024-03-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2024-0004 |
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| author | Pengnam Supusson Jitkaroon Watcharapa Srisuphan Roongtiwa Wongprayoon Pawaris Rayanil Kanok-On Charoensuksai Purin |
| author_facet | Pengnam Supusson Jitkaroon Watcharapa Srisuphan Roongtiwa Wongprayoon Pawaris Rayanil Kanok-On Charoensuksai Purin |
| author_sort | Pengnam Supusson |
| collection | DOAJ |
| description | Although the anticancer activity of Dorstenia foetida was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, i.e., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (1) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate (2) isolated from ethyl acetate fraction of D. foetida (whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound 2 exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound 2 and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri:2 of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound 2 and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound 2 monotherapy, resp). In conclusion, our results identified compound 2 as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment. |
| format | Article |
| id | doaj-art-5e003e2e4eb1499e94eeb413d3b4d571 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-5e003e2e4eb1499e94eeb413d3b4d5712025-02-03T03:22:45ZengSciendoActa Pharmaceutica1846-95582024-03-01741677910.2478/acph-2024-0004Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cellsPengnam Supusson0Jitkaroon Watcharapa1Srisuphan Roongtiwa2Wongprayoon Pawaris3Rayanil Kanok-On4Charoensuksai Purin5Department of Biomedicine and Health Informatics, Green Innovations Group (PDGIG), Faculty of Pharmacy Silpakorn University, Nakhon Pathom 73000, ThailandDepartment of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom, 73000, ThailandBioactives from Natural Resources Research Collaboration for Excellence in Pharmaceutical Sciences (BNEP)Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000ThailandDepartment of Biomedicine and Health Informatics and Bioactives from Natural Resources Research Collaboration for Excellence in Pharmaceutical Sciences (BNEP), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom73000ThailandDepartment of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom, 73000, ThailandDepartment of Biomedicine and Health Informatics and Bioactives from Natural Resources Research Collaboration for Excellence in Pharmaceutical Sciences (BNEP), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom73000ThailandAlthough the anticancer activity of Dorstenia foetida was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, i.e., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (1) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate (2) isolated from ethyl acetate fraction of D. foetida (whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound 2 exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound 2 and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri:2 of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound 2 and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound 2 monotherapy, resp). In conclusion, our results identified compound 2 as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment.https://doi.org/10.2478/acph-2024-00045-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetatefuranocoumarinsanticancer activityirinotecansynergism |
| spellingShingle | Pengnam Supusson Jitkaroon Watcharapa Srisuphan Roongtiwa Wongprayoon Pawaris Rayanil Kanok-On Charoensuksai Purin Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells Acta Pharmaceutica 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate furanocoumarins anticancer activity irinotecan synergism |
| title | Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells |
| title_full | Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells |
| title_fullStr | Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells |
| title_full_unstemmed | Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells |
| title_short | Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells |
| title_sort | furanocoumarin compounds isolated from dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells |
| topic | 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate furanocoumarins anticancer activity irinotecan synergism |
| url | https://doi.org/10.2478/acph-2024-0004 |
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