Cancer Research and Treatment

Original Articles

Head/neck cancer

Protective Effects of N-Acetylcysteine against Radiation-Induced Oral Mucositis In Vitro and In Vivo: Haeng Jun Kim, Sung Un Kang, Yun Sang Lee, Jeon Yeob Jang, Hami Kang, Chul-Ho Kim; Cancer Res Treat. 2020;52(4):1019-1030. Published online June 18, 2020; DOI: https://doi.org/10.4143/crt.2020.012

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Purpose
Radiation-induced oral mucositis limits delivery of high-dose radiation to targeted cancers. Therefore, it is necessary to develop a treatment strategy to alleviate radiation-induced oral mucositis during radiation therapy. We previously reported that inhibiting reactive oxygen species (ROS) generation suppresses autophagy. Irradiation induces autophagy, suggesting that antioxidant treatment may be used to inhibit radiation-induced oral mucositis.
Materials and Methods
We determined whether treatment with N-acetyl cysteine (NAC) could attenuate radiation-induced buccal mucosa damage in vitro and in vivo. The protective effects of NAC against oral mucositis were confirmed by transmission electron microscopy and immunocytochemistry. mRNA and protein levels of DNA damage and autophagy-related genes were measured by quantitative real-time polymerase chain reaction and western blot analysis, respectively.
Results
Rats manifesting radiation-induced oral mucositis showed decreased oral intake, loss of body weight, and low survival rate. NAC intake slightly increased oral intake, body weight, and the survival rate without statistical significance. However, histopathologic characteristics were markedly restored in NAC-treated irradiated rats. LC3B staining of rat buccal mucosa revealed that NAC treatment significantly decreased the number of radiation-induced autophagic cells. Further, NAC inhibited radiation-induced ROS generation and autophagy signaling. In vitro, NAC treatment significantly reduced the expression of NRF2, LC3B, p62, and Beclin-1 in keratinocytes compared with that after radiation treatment.
Conclusion
NAC treatment significantly inhibited radiation-induced autophagy in keratinocytes and rat buccal mucosa and may be a potentially safe and effective option for the prevention of radiation-induced buccal mucosa damage.

Citations

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N-Acetyl-L-Cysteine Protects Organ Function After Hemorrhagic Shock Combined With Seawater Immersion in Rats by Correcting Coagulopathy and Acidosis
Yiyan Liu, Yu Zhu, Zisen Zhang, Daiqin Bao, Haoyue Deng, Liangming Liu, Tao Li
Frontiers in Physiology.2022;[Epub] CrossRef
Nutraceuticals as Modulators of Autophagy: Relevance in Parkinson’s Disease
Michał Rakowski, Szymon Porębski, Agnieszka Grzelak
International Journal of Molecular Sciences.2022; 23(7): 3625. CrossRef
Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies
Huynh Nguyen, Simran Sangha, Michelle Pan, Dong Ha Shin, Hayoung Park, Ali I. Mohammed, Nicola Cirillo
International Journal of Molecular Sciences.2022; 23(9): 4863. CrossRef
A Minireview on Gastrointestinal Microbiota and Radiosusceptibility
Aihong Mao, Chao Sun, Takanori Katsube, Bing Wang
Dose-Response.2020;[Epub] CrossRef

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265 Download
11 Web of Science
4 Crossref

Anti-cancer Effect of Luminacin, a Marine Microbial Extract, in Head and Neck Squamous Cell Carcinoma Progression via Autophagic Cell Death: Yoo Seob Shin, Hyun Young Cha, Bok-Soon Lee, Sung Un Kang, Hye Sook Hwang, Hak Cheol Kwon, Chul-Ho Kim, Eun Chang Choi; Cancer Res Treat. 2016;48(2):738-752. Published online September 9, 2015; DOI: https://doi.org/10.4143/crt.2015.102

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to determine whether luminacin, a marine microbial extract from the Streptomyces species, has anti-tumor effects on head and neck squamous cell carcinoma (HNSCC) cell lines via autophagic cell death. Materials and Methods Inhibition of cell survival and increased cell death was measured using cell viability, colony forming, and apoptosis assays. Migration and invasion abilities of head and cancer cells were evaluated using wound healing, scattering, and invasion assays. Changes in the signal pathway related to autophagic cell death were investigated. Drug toxicity of luminacin was examined in in vitro HaCaT cells and an in vivo zebrafish model.
Results
Luminacin showed potent cytotoxicity in HNSCC cells in cell viability, colony forming, and fluorescence-activated cell sorting analysis. In vitro migration and invasion of HNSCC cells were attenuated by luminacin treatment. Combined with Beclin-1 and LC3B, Luminacin induced autophagic cell death in head and neck cancer cells. In addition, in a zebrafish model and human keratinocyte cell line used for toxicity testing, luminacin treatment with a cytotoxic concentration to HNSCC cells did not cause toxicity. Conclusion Taken together, these results demonstrate that luminacin induces the inhibition of growth and cancer progression via autophagic cell death in HNSCC cell lines, indicating a possible alternative chemotherapeutic approach for treatment of HNSCC.

Citations

Citations to this article as recorded by

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Autophagy-Related Beclin 1 and Head and Neck Cancers

Yang-Jie Hu, Jiang-Tao Zhong, Liang Gong, Si-Cong Zhang, Shui-Hong Zhou
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Non-thermal plasma inhibits mast cell activation and ameliorates allergic skin inflammatory diseases in NC/Nga mice
Myung-Hoon Lee, Yun Sang Lee, Haeng Jun Kim, Chang Hak Han, Sung Un Kang, Chul-Ho Kim
Scientific Reports.2019;[Epub] CrossRef
HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer
Sun-Yong Kim, Hyo Jeong Kim, Haeng-Jun Kim, Dae Ho Kim, Jae Ho Han, Hyung Kwon Byeon, Keunho Lee, Chul-Ho Kim
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13,379 View
167 Download
18 Web of Science
16 Crossref

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