Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells
Despite the relative effectiveness of standard cancer treatment strategies, head and neck cancer (HNC) is still considered one of the leading causes of mortality and morbidity. While selected bioactive compounds of plant origin reveal a pro-apoptotic effect, kaempferol and fisetin flavonols have bee...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/12/1568 |
| _version_ | 1797595589438865408 |
|---|---|
| author | Robert Kubina Kamil Krzykawski Arkadiusz Dziedzic Agata Kabała-Dzik |
| author_facet | Robert Kubina Kamil Krzykawski Arkadiusz Dziedzic Agata Kabała-Dzik |
| author_sort | Robert Kubina |
| collection | DOAJ |
| description | Despite the relative effectiveness of standard cancer treatment strategies, head and neck cancer (HNC) is still considered one of the leading causes of mortality and morbidity. While selected bioactive compounds of plant origin reveal a pro-apoptotic effect, kaempferol and fisetin flavonols have been reported as potential anti-cancer agents against malignant neoplasms. To date, their exact role in signaling pathways of head and neck cancer cells is largely unknown. Based on the various methods of cytotoxicity testing, we elucidated that kaempferol and fisetin inhibit proliferation, reduce the capacity of cell migration, and induce apoptosis in SCC-9, SCC-25, and A-253 HNC cells in a dose-dependent manner in vitro (<i>p</i> < 0.05, fisetin IC<sub>50</sub> values of 38.85 µM, 62.34 µM, and 49.21 µM, and 45.03 µM, 49.90 µM, and 47.49 µM for kaempferol–SCC-9, SCC-25, and A-253, respectively). The obtained results showed that exposure to kaempferol and fisetin reduces Bcl-2 protein expression, simultaneously leading to the arrest in the G2/M and S phases of the cell cycle. Kaempferol and fisetin inhibit cell proliferation by interfering with the cell cycle, which is strongly associated with the induction of G2/M arrest, and induce apoptosis by activating caspase-3 and releasing cytochrome c in human HNC cells. In addition, investigating flavonols, by inhibiting anti-apoptotic proteins from the Bcl-2 family and damaging the mitochondrial transmembrane potential, increased the level of cytochrome c. While flavonols selectively induce apoptosis of head and neck cancer cells, they may support oncological therapy as promising agents. The discovery of new derivatives may be a breakthrough in the search for effective chemotherapeutic agents with less toxicity and thus fewer side effects. |
| first_indexed | 2024-03-11T02:38:44Z |
| format | Article |
| id | doaj.art-4f17780873034a9897101cfd45a259a9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T02:38:44Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4f17780873034a9897101cfd45a259a92023-11-18T09:42:50ZengMDPI AGCells2073-44092023-06-011212156810.3390/cells12121568Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer CellsRobert Kubina0Kamil Krzykawski1Arkadiusz Dziedzic2Agata Kabała-Dzik3Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 30 Ostrogórska Str., 41-200 Sosnowiec, PolandSilesia LabMed, Centre for Research and Implementation, Medical University of Silesia in Katowice, 18 Medyków Str., 40-752 Katowice, PolandDepartment of Conservative Dentistry with Endodontics, Medical University of Silesia, 40-055 Katowice, PolandDepartment of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 30 Ostrogórska Str., 41-200 Sosnowiec, PolandDespite the relative effectiveness of standard cancer treatment strategies, head and neck cancer (HNC) is still considered one of the leading causes of mortality and morbidity. While selected bioactive compounds of plant origin reveal a pro-apoptotic effect, kaempferol and fisetin flavonols have been reported as potential anti-cancer agents against malignant neoplasms. To date, their exact role in signaling pathways of head and neck cancer cells is largely unknown. Based on the various methods of cytotoxicity testing, we elucidated that kaempferol and fisetin inhibit proliferation, reduce the capacity of cell migration, and induce apoptosis in SCC-9, SCC-25, and A-253 HNC cells in a dose-dependent manner in vitro (<i>p</i> < 0.05, fisetin IC<sub>50</sub> values of 38.85 µM, 62.34 µM, and 49.21 µM, and 45.03 µM, 49.90 µM, and 47.49 µM for kaempferol–SCC-9, SCC-25, and A-253, respectively). The obtained results showed that exposure to kaempferol and fisetin reduces Bcl-2 protein expression, simultaneously leading to the arrest in the G2/M and S phases of the cell cycle. Kaempferol and fisetin inhibit cell proliferation by interfering with the cell cycle, which is strongly associated with the induction of G2/M arrest, and induce apoptosis by activating caspase-3 and releasing cytochrome c in human HNC cells. In addition, investigating flavonols, by inhibiting anti-apoptotic proteins from the Bcl-2 family and damaging the mitochondrial transmembrane potential, increased the level of cytochrome c. While flavonols selectively induce apoptosis of head and neck cancer cells, they may support oncological therapy as promising agents. The discovery of new derivatives may be a breakthrough in the search for effective chemotherapeutic agents with less toxicity and thus fewer side effects.https://www.mdpi.com/2073-4409/12/12/1568fisetinkaempferolapoptosishead and neck cancercell cyclecaspase-3 |
| spellingShingle | Robert Kubina Kamil Krzykawski Arkadiusz Dziedzic Agata Kabała-Dzik Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells Cells fisetin kaempferol apoptosis head and neck cancer cell cycle caspase-3 |
| title | Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells |
| title_full | Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells |
| title_fullStr | Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells |
| title_full_unstemmed | Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells |
| title_short | Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells |
| title_sort | kaempferol and fisetin related signaling pathways induce apoptosis in head and neck cancer cells |
| topic | fisetin kaempferol apoptosis head and neck cancer cell cycle caspase-3 |
| url | https://www.mdpi.com/2073-4409/12/12/1568 |
| work_keys_str_mv | AT robertkubina kaempferolandfisetinrelatedsignalingpathwaysinduceapoptosisinheadandneckcancercells AT kamilkrzykawski kaempferolandfisetinrelatedsignalingpathwaysinduceapoptosisinheadandneckcancercells AT arkadiuszdziedzic kaempferolandfisetinrelatedsignalingpathwaysinduceapoptosisinheadandneckcancercells AT agatakabaładzik kaempferolandfisetinrelatedsignalingpathwaysinduceapoptosisinheadandneckcancercells |