Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro
A novel nitrated [6,6,6]tricycles-derived compound containing nitro, methoxy, and ispropyloxy groups, namely SK1, was developed in our previous report. However, the anticancer effects of SK1 were not assessed. Moreover, SK1 contains two nitro groups (NO<sub>2</sub>) and one nitrogen-oxyg...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/10/2072 |
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| author | Yan-Ning Chen Chieh-Kai Chan Ching-Yu Yen Jun-Ping Shiau Meng-Yang Chang Cheng-Chung Wang Jiiang-Huei Jeng Jen-Yang Tang Hsueh-Wei Chang |
| author_facet | Yan-Ning Chen Chieh-Kai Chan Ching-Yu Yen Jun-Ping Shiau Meng-Yang Chang Cheng-Chung Wang Jiiang-Huei Jeng Jen-Yang Tang Hsueh-Wei Chang |
| author_sort | Yan-Ning Chen |
| collection | DOAJ |
| description | A novel nitrated [6,6,6]tricycles-derived compound containing nitro, methoxy, and ispropyloxy groups, namely SK1, was developed in our previous report. However, the anticancer effects of SK1 were not assessed. Moreover, SK1 contains two nitro groups (NO<sub>2</sub>) and one nitrogen-oxygen (N-O) bond exhibiting the potential for oxidative stress generation, but this was not examined. The present study aimed to evaluate the antiproliferation effects and oxidative stress and its associated responses between oral cancer and normal cells. Based on the MTS assay, SK1 demonstrated more antiproliferation ability in oral cancer cells than normal cells, reversed by <i>N</i>-acetylcysteine. This suggests that SK1 causes antiproliferation effects preferentially in an oxidative stress-dependent manner. The oxidative stress-associated responses were further validated, showing higher ROS/MitoSOX burst, MMP, and GSH depletion in oral cancer cells than in normal cells. Meanwhile, SK1 caused oxidative stress-causing apoptosis, such as caspases 3/8/9, and DNA damages, such as γH2AX and 8-OHdG, to a greater extent in oral cancer cells than in normal cells. Siilar to cell viability, these oxidative stress responses were partially diminished by NAC, indicating that SK1 promoted oxidative stress-dependent responses. In conclusion, SK1 exerts oxidative stress, apoptosis, and DNA damage to a greater extent to oral cancer cells than in normal cells. |
| first_indexed | 2024-03-09T20:48:55Z |
| format | Article |
| id | doaj.art-c61927ca906d48bc96b6c2d0c777b260 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T20:48:55Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c61927ca906d48bc96b6c2d0c777b2602023-11-23T22:40:21ZengMDPI AGAntioxidants2076-39212022-10-011110207210.3390/antiox11102072Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In VitroYan-Ning Chen0Chieh-Kai Chan1Ching-Yu Yen2Jun-Ping Shiau3Meng-Yang Chang4Cheng-Chung Wang5Jiiang-Huei Jeng6Jen-Yang Tang7Hsueh-Wei Chang8Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanInstitute of Chemistry, Academia Sinica, Taipei 115024, TaiwanSchool of Dentistry, Taipei Medical University, Taipei 11031, TaiwanDivision of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, TaiwanInstitute of Chemistry, Academia Sinica, Taipei 115024, TaiwanSchool of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanA novel nitrated [6,6,6]tricycles-derived compound containing nitro, methoxy, and ispropyloxy groups, namely SK1, was developed in our previous report. However, the anticancer effects of SK1 were not assessed. Moreover, SK1 contains two nitro groups (NO<sub>2</sub>) and one nitrogen-oxygen (N-O) bond exhibiting the potential for oxidative stress generation, but this was not examined. The present study aimed to evaluate the antiproliferation effects and oxidative stress and its associated responses between oral cancer and normal cells. Based on the MTS assay, SK1 demonstrated more antiproliferation ability in oral cancer cells than normal cells, reversed by <i>N</i>-acetylcysteine. This suggests that SK1 causes antiproliferation effects preferentially in an oxidative stress-dependent manner. The oxidative stress-associated responses were further validated, showing higher ROS/MitoSOX burst, MMP, and GSH depletion in oral cancer cells than in normal cells. Meanwhile, SK1 caused oxidative stress-causing apoptosis, such as caspases 3/8/9, and DNA damages, such as γH2AX and 8-OHdG, to a greater extent in oral cancer cells than in normal cells. Siilar to cell viability, these oxidative stress responses were partially diminished by NAC, indicating that SK1 promoted oxidative stress-dependent responses. In conclusion, SK1 exerts oxidative stress, apoptosis, and DNA damage to a greater extent to oral cancer cells than in normal cells.https://www.mdpi.com/2076-3921/11/10/2072nitrated [6,6,6]tricyclesoral cancer cellsoxidative stressapoptosisDNA damage |
| spellingShingle | Yan-Ning Chen Chieh-Kai Chan Ching-Yu Yen Jun-Ping Shiau Meng-Yang Chang Cheng-Chung Wang Jiiang-Huei Jeng Jen-Yang Tang Hsueh-Wei Chang Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro Antioxidants nitrated [6,6,6]tricycles oral cancer cells oxidative stress apoptosis DNA damage |
| title | Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro |
| title_full | Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro |
| title_fullStr | Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro |
| title_full_unstemmed | Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro |
| title_short | Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro |
| title_sort | antioral cancer effects by the nitrated 6 6 6 tricycles compound sk1 in vitro |
| topic | nitrated [6,6,6]tricycles oral cancer cells oxidative stress apoptosis DNA damage |
| url | https://www.mdpi.com/2076-3921/11/10/2072 |
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