Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways
Abstract Background TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, can selectively kill cancer cells with little or no cytotoxicity toward normal human cells and is regarded as a potential relatively safe antitumor drug. However, some cancer cells are resistant to TRAIL-induced apop...
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | BMC Cell Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s12860-018-0179-7 |
| _version_ | 1818321669335285760 |
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| author | Zhi Lan Guo Jing Zhe Li Yan Yan Ma Dan Qian Ju Ying Zhong Meng Meng Jin Peng Huang Lu Yang Che Bing Pan Yi Wang Zhen Xiao Sun Chang Zhen Liu |
| author_facet | Zhi Lan Guo Jing Zhe Li Yan Yan Ma Dan Qian Ju Ying Zhong Meng Meng Jin Peng Huang Lu Yang Che Bing Pan Yi Wang Zhen Xiao Sun Chang Zhen Liu |
| author_sort | Zhi Lan Guo |
| collection | DOAJ |
| description | Abstract Background TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, can selectively kill cancer cells with little or no cytotoxicity toward normal human cells and is regarded as a potential relatively safe antitumor drug. However, some cancer cells are resistant to TRAIL-induced apoptosis. Thus, reagents that potentiate TRAIL-induced cytotoxicity are needed. Herein, we investigated whether shikonin, a natural compound from the root of Lithospermum erythrorhizon, can sensitize TRAIL-resistant cells to TRAIL-induced cytotoxicity. Results The viability of A549 cells, which were resistant to TRAIL, was significantly decreased after treatment with TRAIL followed by shikonin. The underlying mechanisms by which shikonin sensitizes cells to TRAIL-induced cytotoxicity were also examined. Combined treatment with shikonin and TRAIL activated the caspase and JNK pathways, inhibited the STAT3 and AKT pathways, downregulated the expression of Mcl-1, Bcl-2, Bcl-xL, c-FLIP and XIAP and upregulated the expression of Bid. Conclusions In conclusion, the results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins. |
| first_indexed | 2024-12-13T10:44:34Z |
| format | Article |
| id | doaj.art-9efb4006c4f444588c0ebc102f89e71e |
| institution | Directory Open Access Journal |
| issn | 1471-2121 |
| language | English |
| last_indexed | 2024-12-13T10:44:34Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cell Biology |
| spelling | doaj.art-9efb4006c4f444588c0ebc102f89e71e2022-12-21T23:50:17ZengBMCBMC Cell Biology1471-21212018-12-011911810.1186/s12860-018-0179-7Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathwaysZhi Lan Guo0Jing Zhe Li1Yan Yan Ma2Dan Qian3Ju Ying Zhong4Meng Meng Jin5Peng Huang6Lu Yang Che7Bing Pan8Yi Wang9Zhen Xiao Sun10Chang Zhen Liu11College of Chinese Pharmacy, Beijing University of Chinese MedicineBeijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesDepartment of Geriatric Endocrinology, The General Hospital of Chinese People’s Liberation ArmyDepartment of Orthopaedics, The General Hospital of Chinese People’s Liberation ArmyDepartment of Orthopaedics, The General Hospital of Chinese People’s Liberation ArmyBeijing Jiquan Biology Technology Co Ltd.Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesCollege of Chinese Pharmacy, Beijing University of Chinese MedicineBeijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesAbstract Background TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, can selectively kill cancer cells with little or no cytotoxicity toward normal human cells and is regarded as a potential relatively safe antitumor drug. However, some cancer cells are resistant to TRAIL-induced apoptosis. Thus, reagents that potentiate TRAIL-induced cytotoxicity are needed. Herein, we investigated whether shikonin, a natural compound from the root of Lithospermum erythrorhizon, can sensitize TRAIL-resistant cells to TRAIL-induced cytotoxicity. Results The viability of A549 cells, which were resistant to TRAIL, was significantly decreased after treatment with TRAIL followed by shikonin. The underlying mechanisms by which shikonin sensitizes cells to TRAIL-induced cytotoxicity were also examined. Combined treatment with shikonin and TRAIL activated the caspase and JNK pathways, inhibited the STAT3 and AKT pathways, downregulated the expression of Mcl-1, Bcl-2, Bcl-xL, c-FLIP and XIAP and upregulated the expression of Bid. Conclusions In conclusion, the results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins.http://link.springer.com/article/10.1186/s12860-018-0179-7ShikoninTRAILResistant cancersSensitization |
| spellingShingle | Zhi Lan Guo Jing Zhe Li Yan Yan Ma Dan Qian Ju Ying Zhong Meng Meng Jin Peng Huang Lu Yang Che Bing Pan Yi Wang Zhen Xiao Sun Chang Zhen Liu Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways BMC Cell Biology Shikonin TRAIL Resistant cancers Sensitization |
| title | Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways |
| title_full | Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways |
| title_fullStr | Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways |
| title_full_unstemmed | Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways |
| title_short | Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways |
| title_sort | shikonin sensitizes a549 cells to trail induced apoptosis through the jnk stat3 and akt pathways |
| topic | Shikonin TRAIL Resistant cancers Sensitization |
| url | http://link.springer.com/article/10.1186/s12860-018-0179-7 |
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