Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway
Abstract Background Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cel...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-023-01420-z |
| _version_ | 1797647355835580416 |
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| author | Xiang Zheng Lei Yang Wei Zhai Nana Geng Zhimin Zhang Xueying Li Mingsong Wu |
| author_facet | Xiang Zheng Lei Yang Wei Zhai Nana Geng Zhimin Zhang Xueying Li Mingsong Wu |
| author_sort | Xiang Zheng |
| collection | DOAJ |
| description | Abstract Background Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis. Methods Cell lines were treated with CDDP, TA, and CDDP + TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the levels of ERS apoptosis pathway related genes were valuated by qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated. Results The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP + TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest, and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher. Conclusions The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer. |
| first_indexed | 2024-03-11T15:16:08Z |
| format | Article |
| id | doaj.art-ba3dc3e5f82942cca0abf58f4fccd982 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-11T15:16:08Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-ba3dc3e5f82942cca0abf58f4fccd9822023-10-29T12:18:33ZengBMCEuropean Journal of Medical Research2047-783X2023-10-0128111410.1186/s40001-023-01420-zSynergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathwayXiang Zheng0Lei Yang1Wei Zhai2Nana Geng3Zhimin Zhang4Xueying Li5Mingsong Wu6Department of Genetics, Zunyi Medical University, Xinpu CampusDepartment of Genetics, Zunyi Medical University, Xinpu CampusDepartment of Genetics, Zunyi Medical University, Xinpu CampusSchool of Stomatology, Zunyi Medical University, Xinpu CampusDepartment of Genetics, Zunyi Medical University, Xinpu CampusDepartment of Genetics, Zunyi Medical University, Xinpu CampusSchool of Stomatology, Zunyi Medical University, Xinpu CampusAbstract Background Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis. Methods Cell lines were treated with CDDP, TA, and CDDP + TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the levels of ERS apoptosis pathway related genes were valuated by qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated. Results The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP + TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest, and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher. Conclusions The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.https://doi.org/10.1186/s40001-023-01420-zLung cancerEndoplasmic reticulum stressTanninsCisplatinCombination drugs |
| spellingShingle | Xiang Zheng Lei Yang Wei Zhai Nana Geng Zhimin Zhang Xueying Li Mingsong Wu Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway European Journal of Medical Research Lung cancer Endoplasmic reticulum stress Tannins Cisplatin Combination drugs |
| title | Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway |
| title_full | Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway |
| title_fullStr | Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway |
| title_full_unstemmed | Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway |
| title_short | Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway |
| title_sort | synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the perk atf4 pathway |
| topic | Lung cancer Endoplasmic reticulum stress Tannins Cisplatin Combination drugs |
| url | https://doi.org/10.1186/s40001-023-01420-z |
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