Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells
Abstract Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevert...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01591-y |
| _version_ | 1797453880986959872 |
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| author | Sun-Hyok Kong Lie Ma Qingxia Yuan Xiangxiang Liu Yu Han Weifang Xiang Dong-Xu Liu Yu Zhang Jun Lu |
| author_facet | Sun-Hyok Kong Lie Ma Qingxia Yuan Xiangxiang Liu Yu Han Weifang Xiang Dong-Xu Liu Yu Zhang Jun Lu |
| author_sort | Sun-Hyok Kong |
| collection | DOAJ |
| description | Abstract Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevertheless, the senescence-associated secretion phenotype (SASP) promotes chronic inflammation of the cancer microenvironment and further accelerates the progression of tumors. Therefore, inducing the senescence of cancer cells and inhibiting the production of SASP factors during anticancer treatment have become effective therapeutic strategies to improve the anticancer effect of drugs. Here we reported that SCLC cells treated with an FDA-approved HDAC inhibitor SAHA underwent senescence and displayed remarkable SASP. In particular, SAHA promoted the formation of cytoplasmic chromatin fragments (CCFs) in SCLC cells. The increased CCFs in SAHA-treated SCLC cells were related to nuclear porin Tpr, which activated the cGAS-STING pathway, and promoted the secretion of SASP in cancer cells. Inhibition of EZH2 suppressed the increase of CCFs in SAHA-treated SCLC cells, weakened the production of SASP, and increased the antiproliferative effect of SAHA. Overall, our work affords new insight into the secretion of SASP in SCLC and establishes a foundation for constructing a new therapeutic strategy for SCLC patients. |
| first_indexed | 2024-03-09T15:29:16Z |
| format | Article |
| id | doaj.art-6287bb6c5a754a2099d9ae4b45667064 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-09T15:29:16Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-6287bb6c5a754a2099d9ae4b456670642023-11-26T12:21:28ZengNature Publishing GroupCell Death Discovery2058-77162023-08-019111210.1038/s41420-023-01591-yInhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cellsSun-Hyok Kong0Lie Ma1Qingxia Yuan2Xiangxiang Liu3Yu Han4Weifang Xiang5Dong-Xu Liu6Yu Zhang7Jun Lu8The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal UniversityThe Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal UniversityThe Institute of Genetics and Cytology, Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal UniversityThe Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal UniversityThe Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of TechnologyThe Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal UniversityThe Institute of Genetics and Cytology, Northeast Normal UniversityAbstract Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevertheless, the senescence-associated secretion phenotype (SASP) promotes chronic inflammation of the cancer microenvironment and further accelerates the progression of tumors. Therefore, inducing the senescence of cancer cells and inhibiting the production of SASP factors during anticancer treatment have become effective therapeutic strategies to improve the anticancer effect of drugs. Here we reported that SCLC cells treated with an FDA-approved HDAC inhibitor SAHA underwent senescence and displayed remarkable SASP. In particular, SAHA promoted the formation of cytoplasmic chromatin fragments (CCFs) in SCLC cells. The increased CCFs in SAHA-treated SCLC cells were related to nuclear porin Tpr, which activated the cGAS-STING pathway, and promoted the secretion of SASP in cancer cells. Inhibition of EZH2 suppressed the increase of CCFs in SAHA-treated SCLC cells, weakened the production of SASP, and increased the antiproliferative effect of SAHA. Overall, our work affords new insight into the secretion of SASP in SCLC and establishes a foundation for constructing a new therapeutic strategy for SCLC patients.https://doi.org/10.1038/s41420-023-01591-y |
| spellingShingle | Sun-Hyok Kong Lie Ma Qingxia Yuan Xiangxiang Liu Yu Han Weifang Xiang Dong-Xu Liu Yu Zhang Jun Lu Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells Cell Death Discovery |
| title | Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells |
| title_full | Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells |
| title_fullStr | Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells |
| title_full_unstemmed | Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells |
| title_short | Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells |
| title_sort | inhibition of ezh2 alleviates saha induced senescence associated secretion phenotype in small cell lung cancer cells |
| url | https://doi.org/10.1038/s41420-023-01591-y |
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