Oxidative Stress-Dependent Synergistic Antiproliferation, Apoptosis, and DNA Damage of Ultraviolet-C and Coral-Derived Sinularin Combined Treatment for Oral Cancer Cells
| Autor: | Hurng-Wern Huang, Fang Rong Chang, Ruei-Nian Li, Chang-Yi Wu, Jen-Yang Tang, Chien-Chih Chiu, Yun-Jou Lee, Sheng-Yao Peng, Jyh-Horng Sheu, Hong-Wei Zhang, Hsueh-Wei Chang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research DNA damage Caspase 3 medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Annexin medicine combined treatment oxidative stress Viability assay sinularin coral RC254-282 chemistry.chemical_classification Reactive oxygen species apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens oral cancer 030104 developmental biology Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Cancer cell Cancer research UVC Oxidative stress |
| Zdroj: | Cancers Volume 13 Issue 10 Cancers, Vol 13, Iss 2450, p 2450 (2021) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13102450 |
| Popis: | Simple Summary Combined treatments with low side effects enhance anticancer applications. This study focusses on validating the potential synergistic antiproliferation of the combined treatment of ultraviolet-C and the coral-derived compound sinularin (UVC/sinularin) in oral cancer cells. This study confirms that UVC/sinularin synergistically and selectively inhibits oral cancer cell proliferation with low cytotoxicity on normal oral cells. The mechanisms involve the enhanced cellular and mitochondrial oxidative stress that cause apoptosis, DNA damage, and mitochondrial dysfunction in oral cancer cells. Abstract Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment of UVC/sinularin has not been investigated as yet. This study aimed to examine the combined antiproliferation function and explore the combination of UVC/sinularin in oral cancer cells compared to normal oral cells. Regarding cell viability, UVC/sinularin displays the synergistic and selective killing of two oral cancer cell lines, but remains non-effective for normal oral cell lines compared to treatments in terms of MTS and ATP assays. In tests using the flow cytometry, luminescence, and Western blotting methods, UVC/sinularin-treated oral cancer cells exhibited higher reactive oxygen species production, mitochondrial superoxide generation, mitochondrial membrane potential destruction, annexin V, pan-caspase, caspase 3/7, and cleaved-poly (ADP-ribose) polymerase expressions than that in normal oral cells. Accordingly, oxidative stress and apoptosis are highly induced in a combined UVC/sinularin treatment. Moreover, UVC/sinularin treatment provides higher G2/M arrest and γH2AX/8-hydroxyl-2′deoxyguanosine-detected DNA damages in oral cancer cells than in the separate treatments. A pretreatment can revert all of these changes of UVC/sinularin treatment with the antioxidant N-acetylcysteine. Taken together, UVC/sinularin acting upon oral cancer cells exhibits a synergistic and selective antiproliferation ability involving oxidative stress-dependent apoptosis and cellular DNA damage with low toxic side effects on normal oral cells. |
| Databáze: | OpenAIRE |
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