Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma
Abstract During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HC...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05771-7 |
| _version_ | 1797845745781440512 |
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| author | Ye Yang Ming Jin Yajie Meng Yi Dai Shuai Chen Yan Zhou Yuan Li Liming Tang |
| author_facet | Ye Yang Ming Jin Yajie Meng Yi Dai Shuai Chen Yan Zhou Yuan Li Liming Tang |
| author_sort | Ye Yang |
| collection | DOAJ |
| description | Abstract During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in. |
| first_indexed | 2024-04-09T17:43:54Z |
| format | Article |
| id | doaj.art-6527b52299744072bb566690f81774fb |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-09T17:43:54Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6527b52299744072bb566690f81774fb2023-04-16T11:26:43ZengNature Publishing GroupCell Death and Disease2041-48892023-04-0114411010.1038/s41419-023-05771-7Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinomaYe Yang0Ming Jin1Yajie Meng2Yi Dai3Shuai Chen4Yan Zhou5Yuan Li6Liming Tang7The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical UniversityThe Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical UniversityThe Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical UniversityThe Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityThe Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical UniversityThe Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityAbstract During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.https://doi.org/10.1038/s41419-023-05771-7 |
| spellingShingle | Ye Yang Ming Jin Yajie Meng Yi Dai Shuai Chen Yan Zhou Yuan Li Liming Tang Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma Cell Death and Disease |
| title | Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma |
| title_full | Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma |
| title_fullStr | Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma |
| title_full_unstemmed | Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma |
| title_short | Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma |
| title_sort | involvement and targeted intervention of benzo a pyrene regulated apoptosis related proteome modification and muti drug resistance in hepatocellular carcinoma |
| url | https://doi.org/10.1038/s41419-023-05771-7 |
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