Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells
The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an <i>n</i>-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. T...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/5/1576 |
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| author | Sheng-Chieh Wang Meng-Yang Chang Jun-Ping Shiau Ammad Ahmad Farooqi Yu-Hsiang Huang Jen-Yang Tang Hsueh-Wei Chang |
| author_facet | Sheng-Chieh Wang Meng-Yang Chang Jun-Ping Shiau Ammad Ahmad Farooqi Yu-Hsiang Huang Jen-Yang Tang Hsueh-Wei Chang |
| author_sort | Sheng-Chieh Wang |
| collection | DOAJ |
| description | The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an <i>n</i>-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage. |
| first_indexed | 2024-03-09T20:30:25Z |
| format | Article |
| id | doaj.art-be4e13ed24b64a8283a6a2daa584e8f0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T20:30:25Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-be4e13ed24b64a8283a6a2daa584e8f02023-11-23T23:26:32ZengMDPI AGMolecules1420-30492022-02-01275157610.3390/molecules27051576Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer CellsSheng-Chieh Wang0Meng-Yang Chang1Jun-Ping Shiau2Ammad Ahmad Farooqi3Yu-Hsiang Huang4Jen-Yang Tang5Hsueh-Wei Chang6Department of Biomedical Science and Environmental Biology, Ph.D. Program in Life Sciences, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanInstitute of Biomedical and Genetic Engineering (IBGE), Islamabad 54000, PakistanPost-Graduate Year Training (PGY), Department of Clinical Education and Training, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanSchool of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, Ph.D. Program in Life Sciences, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanThe benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an <i>n</i>-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage.https://www.mdpi.com/1420-3049/27/5/1576nitrated [6,6,6]tricyclesapoptosisDNA damageantiproliferationoral cancer |
| spellingShingle | Sheng-Chieh Wang Meng-Yang Chang Jun-Ping Shiau Ammad Ahmad Farooqi Yu-Hsiang Huang Jen-Yang Tang Hsueh-Wei Chang Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells Molecules nitrated [6,6,6]tricycles apoptosis DNA damage antiproliferation oral cancer |
| title | Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells |
| title_full | Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells |
| title_fullStr | Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells |
| title_full_unstemmed | Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells |
| title_short | Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells |
| title_sort | antiproliferation and apoptosis inducible effects of a novel nitrated 6 6 6 tricycle derivative sk2 on oral cancer cells |
| topic | nitrated [6,6,6]tricycles apoptosis DNA damage antiproliferation oral cancer |
| url | https://www.mdpi.com/1420-3049/27/5/1576 |
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