Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation
The selective antiproliferation to oral cancer cells of <i>Physalis peruviana</i>-derived physapruin A (PHA) is rarely reported. Either drug-induced apoptosis and DNA damage or DNA repair suppression may effectively inhibit cancer cell proliferation. This study examined the selective ant...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8839 |
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| author | Tzu-Jung Yu Ching-Yu Yen Yuan-Bin Cheng Chia-Hung Yen Jiiang-Huei Jeng Jen-Yang Tang Hsueh-Wei Chang |
| author_facet | Tzu-Jung Yu Ching-Yu Yen Yuan-Bin Cheng Chia-Hung Yen Jiiang-Huei Jeng Jen-Yang Tang Hsueh-Wei Chang |
| author_sort | Tzu-Jung Yu |
| collection | DOAJ |
| description | The selective antiproliferation to oral cancer cells of <i>Physalis peruviana</i>-derived physapruin A (PHA) is rarely reported. Either drug-induced apoptosis and DNA damage or DNA repair suppression may effectively inhibit cancer cell proliferation. This study examined the selective antiproliferation ability of PHA and explored detailed mechanisms of apoptosis, DNA damage, and repair. During an ATP assay, PHA provided high cytotoxicity to two oral cancer cell lines (CAL 27 and Ca9-22) but no cytotoxicity to two non-malignant oral cells (HGF-1 and SG). This selective antiproliferation of PHA was associated with the selective generation of reactive oxygen species (ROS) in oral cancer cells rather than in non-malignant oral cells, as detected by flow cytometry. Moreover, PHA induced other oxidative stresses in oral cancer cells, such as mitochondrial superoxide generation and mitochondrial membrane potential depletion. PHA also demonstrated selective apoptosis in oral cancer cells rather than non-malignant cells in annexin V/7-aminoactinmycin D and caspase 3/7 activity assays. In flow cytometry and immunofluorescence assays, PHA induced γH2AX expressions and increased the γH2AX foci number of DNA damages in oral cancer cells. In contrast, the mRNA expressions for DNA repair signaling, including homologous recombination (HR) and non-homologous end joining (NHEJ)-associated genes, were inhibited by PHA in oral cancer cells. Moreover, the PHA-induced changes were alleviated by the oxidative stress inhibitor <i>N</i>-acetylcysteine. Therefore, PHA generates selective antiproliferation, oxidative stress, and apoptosis associated with DNA damage induction and DNA repair suppression in oral cancer cells. |
| first_indexed | 2024-03-09T09:56:39Z |
| format | Article |
| id | doaj.art-be4703cc02fc487c809dbad16a694e34 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T09:56:39Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-be4703cc02fc487c809dbad16a694e342023-12-01T23:46:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316883910.3390/ijms23168839Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell ProliferationTzu-Jung Yu0Ching-Yu Yen1Yuan-Bin Cheng2Chia-Hung Yen3Jiiang-Huei Jeng4Jen-Yang Tang5Hsueh-Wei Chang6Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan 71004, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, TaiwanGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanSchool of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanSchool of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanThe selective antiproliferation to oral cancer cells of <i>Physalis peruviana</i>-derived physapruin A (PHA) is rarely reported. Either drug-induced apoptosis and DNA damage or DNA repair suppression may effectively inhibit cancer cell proliferation. This study examined the selective antiproliferation ability of PHA and explored detailed mechanisms of apoptosis, DNA damage, and repair. During an ATP assay, PHA provided high cytotoxicity to two oral cancer cell lines (CAL 27 and Ca9-22) but no cytotoxicity to two non-malignant oral cells (HGF-1 and SG). This selective antiproliferation of PHA was associated with the selective generation of reactive oxygen species (ROS) in oral cancer cells rather than in non-malignant oral cells, as detected by flow cytometry. Moreover, PHA induced other oxidative stresses in oral cancer cells, such as mitochondrial superoxide generation and mitochondrial membrane potential depletion. PHA also demonstrated selective apoptosis in oral cancer cells rather than non-malignant cells in annexin V/7-aminoactinmycin D and caspase 3/7 activity assays. In flow cytometry and immunofluorescence assays, PHA induced γH2AX expressions and increased the γH2AX foci number of DNA damages in oral cancer cells. In contrast, the mRNA expressions for DNA repair signaling, including homologous recombination (HR) and non-homologous end joining (NHEJ)-associated genes, were inhibited by PHA in oral cancer cells. Moreover, the PHA-induced changes were alleviated by the oxidative stress inhibitor <i>N</i>-acetylcysteine. Therefore, PHA generates selective antiproliferation, oxidative stress, and apoptosis associated with DNA damage induction and DNA repair suppression in oral cancer cells.https://www.mdpi.com/1422-0067/23/16/8839withanolidesoral cancerantiproliferationoxidative stress |
| spellingShingle | Tzu-Jung Yu Ching-Yu Yen Yuan-Bin Cheng Chia-Hung Yen Jiiang-Huei Jeng Jen-Yang Tang Hsueh-Wei Chang Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation International Journal of Molecular Sciences withanolides oral cancer antiproliferation oxidative stress |
| title | Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation |
| title_full | Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation |
| title_fullStr | Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation |
| title_full_unstemmed | Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation |
| title_short | Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation |
| title_sort | physapruin a enhances dna damage and inhibits dna repair to suppress oral cancer cell proliferation |
| topic | withanolides oral cancer antiproliferation oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/16/8839 |
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