Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro
Furanocoumarins are naturally occurring compounds in the plant world, characterized by low molecular weight, simple chemical structure, and high solubility in most organic solvents. Additionally, they have a broad spectrum of activity, and their properties depend on the location and type of attached...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/759 |
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| author | Joanna Sumorek-Wiadro Adrian Zając Krystyna Skalicka-Woźniak Wojciech Rzeski Joanna Jakubowicz-Gil |
| author_facet | Joanna Sumorek-Wiadro Adrian Zając Krystyna Skalicka-Woźniak Wojciech Rzeski Joanna Jakubowicz-Gil |
| author_sort | Joanna Sumorek-Wiadro |
| collection | DOAJ |
| description | Furanocoumarins are naturally occurring compounds in the plant world, characterized by low molecular weight, simple chemical structure, and high solubility in most organic solvents. Additionally, they have a broad spectrum of activity, and their properties depend on the location and type of attached substituents. Therefore, the aim of our study was to investigate the anticancer activity of furanocoumarins (imperatorin, isoimperatorin, bergapten, and xanthotoxin) in relation to human glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cell lines. The tested compounds were used for the first time in combination with LY294002 (PI3K inhibitor) and sorafenib (Raf inhibitor). Apoptosis, autophagy, and necrosis were identified microscopically after straining with Hoechst 33342, acridine orange, and propidium iodide, respectively. The levels of caspase 3 and Beclin 1 were estimated by immunoblotting and for the blocking of Raf and PI3K kinases, the transfection with specific siRNA was used. The scratch test was used to assess the migration potential of glioma cells. Our studies showed that the anticancer activity of furanocoumarins strictly depended on the presence, type, and location of substituents. The obtained results suggest that achieving higher pro-apoptotic activity is determined by the presence of an isoprenyl moiety at the C8 position of the coumarin skeleton. In both anaplastic astrocytoma and glioblastoma, imperatorin was the most effective in induction apoptosis. Furthermore, the usage of imperatorin, alone and in combination with sorafenib or LY294002, decreased the migratory potential of MOGGCCM and T98G cells. |
| first_indexed | 2024-03-08T09:53:49Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:49Z |
| publishDate | 2024-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-66fb2877d37f47d687efea8798f568ab2024-01-29T13:54:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125275910.3390/ijms25020759Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In VitroJoanna Sumorek-Wiadro0Adrian Zając1Krystyna Skalicka-Woźniak2Wojciech Rzeski3Joanna Jakubowicz-Gil4Department of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, PolandDepartment of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, PolandIndependent Laboratory of Natural Products Chemistry, Medical University of Lublin, Chodźki 1, 20-093 Lublin, PolandDepartment of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, PolandDepartment of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, PolandFuranocoumarins are naturally occurring compounds in the plant world, characterized by low molecular weight, simple chemical structure, and high solubility in most organic solvents. Additionally, they have a broad spectrum of activity, and their properties depend on the location and type of attached substituents. Therefore, the aim of our study was to investigate the anticancer activity of furanocoumarins (imperatorin, isoimperatorin, bergapten, and xanthotoxin) in relation to human glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cell lines. The tested compounds were used for the first time in combination with LY294002 (PI3K inhibitor) and sorafenib (Raf inhibitor). Apoptosis, autophagy, and necrosis were identified microscopically after straining with Hoechst 33342, acridine orange, and propidium iodide, respectively. The levels of caspase 3 and Beclin 1 were estimated by immunoblotting and for the blocking of Raf and PI3K kinases, the transfection with specific siRNA was used. The scratch test was used to assess the migration potential of glioma cells. Our studies showed that the anticancer activity of furanocoumarins strictly depended on the presence, type, and location of substituents. The obtained results suggest that achieving higher pro-apoptotic activity is determined by the presence of an isoprenyl moiety at the C8 position of the coumarin skeleton. In both anaplastic astrocytoma and glioblastoma, imperatorin was the most effective in induction apoptosis. Furthermore, the usage of imperatorin, alone and in combination with sorafenib or LY294002, decreased the migratory potential of MOGGCCM and T98G cells.https://www.mdpi.com/1422-0067/25/2/759furanocoumarinsimperatorinisoimperatorinbergaptenxanthotoxingliomas |
| spellingShingle | Joanna Sumorek-Wiadro Adrian Zając Krystyna Skalicka-Woźniak Wojciech Rzeski Joanna Jakubowicz-Gil Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro International Journal of Molecular Sciences furanocoumarins imperatorin isoimperatorin bergapten xanthotoxin gliomas |
| title | Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro |
| title_full | Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro |
| title_fullStr | Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro |
| title_full_unstemmed | Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro |
| title_short | Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro |
| title_sort | furanocoumarins as enhancers of antitumor potential of sorafenib and ly294002 toward human glioma cells in vitro |
| topic | furanocoumarins imperatorin isoimperatorin bergapten xanthotoxin gliomas |
| url | https://www.mdpi.com/1422-0067/25/2/759 |
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