Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells
Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks) is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carrie...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Toxicology Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221475001530024X |
| _version_ | 1818558823844020224 |
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| author | Ji Yeon Lim Joo Yun Lee Byung Jin Byun Seong Hwan Kim |
| author_facet | Ji Yeon Lim Joo Yun Lee Byung Jin Byun Seong Hwan Kim |
| author_sort | Ji Yeon Lim |
| collection | DOAJ |
| description | Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks) is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin’s inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt’s lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR). Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer. |
| first_indexed | 2024-12-14T00:17:19Z |
| format | Article |
| id | doaj.art-4c174a269baf4af5b1ad0436b876b427 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-14T00:17:19Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-4c174a269baf4af5b1ad0436b876b4272022-12-21T23:25:25ZengElsevierToxicology Reports2214-75002015-01-012C98498910.1016/j.toxrep.2015.07.004Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cellsJi Yeon Lim0Joo Yun Lee1Byung Jin Byun2Seong Hwan Kim3Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of KoreaCenter for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of KoreaCenter for Drug Discovery Technology, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of KoreaLaboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of KoreaAberrant regulation of phosphatidylinositol-3-kinases (PI3Ks) is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin’s inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt’s lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR). Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer.http://www.sciencedirect.com/science/article/pii/S221475001530024XPI3KmTORFisetinApoptosisBurkitt’s lymphoma |
| spellingShingle | Ji Yeon Lim Joo Yun Lee Byung Jin Byun Seong Hwan Kim Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells Toxicology Reports PI3K mTOR Fisetin Apoptosis Burkitt’s lymphoma |
| title | Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells |
| title_full | Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells |
| title_fullStr | Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells |
| title_full_unstemmed | Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells |
| title_short | Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells |
| title_sort | fisetin targets phosphatidylinositol 3 kinase and induces apoptosis of human b lymphoma raji cells |
| topic | PI3K mTOR Fisetin Apoptosis Burkitt’s lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S221475001530024X |
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