Reversine Induces Apoptosis of FaDu Hypopharyngeal Carcinoma Cells
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Background: Hypopharyngeal carcinoma is an aggressive subtype of head and neck squamous cell carcinoma, characterized by poor prognosis and resistance to conventional therapies. Reversine, a 2,6-disubstituted purine derivative, exhibits anticancer properties by inducing apoptosis and inhibiting cell proliferation in various cancers. Methods: FaDu hypopharyngeal carcinoma cells were treated with reversine at concentrations of Control, 15 μM, and 30 μM. Cell viability was assessed using MTT and live/dead assays. Apoptotic features were analyzed by hematoxylin & eosin and DAPI staining, and DNA fragmentation assays. Immunoblotting was performed to evaluate caspase-3 and poly adenosine diphosphate-ribose polymerase (PARP) activation. Results: Reversine significantly reduced the viability of FaDu cells in a dose-dependent manner. Morphological changes, nuclear fragmentation, and DNA laddering confirmed apoptosis. Immunoblotting revealed increased levels of cleaved caspase-3 and PARP, indicating the activation of the intrinsic and extrinsic apoptotic pathways. Conclusion: Reversine effectively inhibited FaDu cell viability and induced apoptosis through intrinsic and extrinsic pathways, and represents a potential novel therapeutic agent for hypopharyngeal carcinoma. This study highlights a unique focus on subpharyngeal cancer, overcoming therapeutic resistance, and suggests its potential as an anticancer agent by targeting dual cell death pathways.
Abstract
Background: Hypopharyngeal carcinoma is an aggressive subtype of head and neck squamous cell carcinoma, characterized by poor prognosis and resistance to conventional therapies. Reversine, a 2,6-disubstituted purine derivative, exhibits anticancer properties by inducing apoptosis and inhibiting cell proliferation in various cancers. Methods: FaDu hypopharyngeal carcinoma cells were treated with reversine at concentrations of Control, 15 μM, and 30 μM. Cell viability was assessed using MTT and live/dead assays. Apoptotic features were analyzed by hematoxylin & eosin and DAPI staining, and DNA fragmentation assays. Immunoblotting was performed to evaluate caspase-3 and poly adenosine diphosphate-ribose polymerase (PARP) activation. Results: Reversine significantly reduced the viability of FaDu cells in a dose-dependent manner. Morphological changes, nuclear fragmentation, and DNA laddering confirmed apoptosis. Immunoblotting revealed increased levels of cleaved caspase-3 and PARP, indicating the activation of the intrinsic and extrinsic apoptotic pathways. Conclusion: Reversine effectively inhibited FaDu cell viability and induced apoptosis through intrinsic and extrinsic pathways, and represents a potential novel therapeutic agent for hypopharyngeal carcinoma. This study highlights a unique focus on subpharyngeal cancer, overcoming therapeutic resistance, and suggests its potential as an anticancer agent by targeting dual cell death pathways.
참고문헌 (22)
- Jumaniyazova E, "Role of microenvironmental components in head and neck squamous cell carcinoma", J Pers Med, 13, pp.1616~ (2023)[DOI]
- Jang JY, "Anticancer effects of Ulva compressa extracts on FaDu human hypopharangeal squamous carcinoma cells in vitro", Inter J Oral Biol, 47, pp.41~48 (2022)[DOI]
- Budhiraja G, "Hypopharyngeal squamous cell carcinoma masquaerading as retropharyngeal abscess and presenting as stridor in young male with diabetes mellitus(type I) : a case report", Otolaryngol Case Rep, 21, pp.100327~ (2021)[DOI]
- Jung SY, "Anti-proliferating effect of the extract from some seaweeds against oral carcinoma cell lines", J Korea Contents Assoc, 23, pp.630~638 (2023)[DOI]
- Lim B, "Novel apoptosisinducing agents for the treatment of cancer, a new arsenal in the toolbox", Cancers (Basel), 11, pp.1087~ (2019)[DOI]
- Carlos J, "Reversine exerts cytotoxic effects through multiple cell death mechanisms in acute lymphoblastic leukemia", Cell Oncol(Dordr), 43, pp.1191~1201 (2020)[DOI]
- Kim JS, "Reversine induces caspase-dependent apoptosis of human osteosarcoma cells through extrinsic and intrinsic apoptotic signaling pathways", Genes Genomics, 41, pp.657~665 (2019)[DOI]
- Hu L, "Reversine suppresses osteosarcoma cell growth through targeting BMP-Smad1", 5, Microvasc Res, pp.2021, 135[DOI]
- Xia P, "Reversine inhibits proliferation, invasion and migration and induces cell apoptosis in gastric cancer cells by downregulating TTK", Exp Ther Med, 22, pp.929~ (2021)[DOI]
- Lee YR, "Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy", J Biomed Sci, 19, pp.9~ (2012)[DOI]
- Park YL, "Reversine induces cell cycle arrest and apoptosis via upregulation of the Fas and DR5signaling pathways in human colorectal cancer cells", Int J Oncol, 54, pp.1875~1883 (2019)[DOI]
- Wang S, "Pseudoginsengenin DQ exerts antitumour activity against hypopharyngeal cancer cells by targeting the HIF-1α-GLUT1 pathway", Cancer Cell Int, 21, pp.382~ (2021)[DOI]
- Emmanuel O, "Role of plantderived compounds in immune enhancement against uncontrollable cell proliferation", Brain Behav Immun Integrative, 8, pp.100088~ (2024)[DOI]
- Iglesias-Guimarais V, "Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40", CAD endonuclease, 2012, pp.287, 7766~7779
- Witayateeraporn W, "Aspiletrein A induces apoptosis cell death via increasing reactive oxygen species generation and AMPK activation in non-small-cell lung cancer cells", Int J Mol Sci, 23, pp.9258~ (2022)[DOI]
- Qian S, "The role of BCL-2 family proteins in regulating apoptosis and cancer therapy", Front Oncol, 12, pp.985363~ (2022)[DOI]
- Marto CM, "In vitro characterization of reversine-treated gingival fibroblasts and their safety evaluation after in vivo transplantation", Pharmaceutics, 16, pp.207~ (2024)[DOI]
- Jemaà M, "Reversine inhibits colon carcinoma cell migration by targeting JNK1", Sci Rep, 8, pp.11821~ (2018)[DOI]
- Peng F, "Regulated cell death(RCD)in cancer : key pathways and targeted therapies", Signal Transduct Target Ther, 7, pp.286~ (2022)[DOI]
- Mohammad RM, "Broad targeting of resistance to apoptosis in cancer", Semin Cancer Biol, 35(Suppl), pp.S78~S103 (2015)[DOI]
- Yip HYK, "Signaling pathways in cancer : therapeutic targets, combinatorial treatments, and new developments", Cells, 10, pp.659~ (2021)[DOI]
- Talib WH, "Combination anticancer therapies using selected phytochemicals", Molecules, 27, pp.5452~ (2022)[DOI]