Destruction of the cellular antioxidant pool contributes to resveratrol-induced senescence and apoptosis in lung cancer
Chunhua Liang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorKefan Yi
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorXu Zhou
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorXiaoting Li
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorCaiyun Zhong
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Cancer Research Division, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorCorresponding Author
Hui Cao
Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
Correspondence
Jianyun Zhu, Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Jiangsu 215008, China.
Email: [email protected]
Chunfeng Xie, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing 211166, China.
Email: [email protected]
Hui Cao, Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Chunfeng Xie
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Correspondence
Jianyun Zhu, Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Jiangsu 215008, China.
Email: [email protected]
Chunfeng Xie, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing 211166, China.
Email: [email protected]
Hui Cao, Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jianyun Zhu
Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
Correspondence
Jianyun Zhu, Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Jiangsu 215008, China.
Email: [email protected]
Chunfeng Xie, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing 211166, China.
Email: [email protected]
Hui Cao, Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Email: [email protected]
Search for more papers by this authorChunhua Liang
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorKefan Yi
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorXu Zhou
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorXiaoting Li
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorCaiyun Zhong
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Cancer Research Division, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Search for more papers by this authorCorresponding Author
Hui Cao
Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
Correspondence
Jianyun Zhu, Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Jiangsu 215008, China.
Email: [email protected]
Chunfeng Xie, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing 211166, China.
Email: [email protected]
Hui Cao, Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Chunfeng Xie
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
Correspondence
Jianyun Zhu, Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Jiangsu 215008, China.
Email: [email protected]
Chunfeng Xie, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing 211166, China.
Email: [email protected]
Hui Cao, Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jianyun Zhu
Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
Correspondence
Jianyun Zhu, Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Jiangsu 215008, China.
Email: [email protected]
Chunfeng Xie, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing 211166, China.
Email: [email protected]
Hui Cao, Department of Thoracic Surgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Email: [email protected]
Search for more papers by this authorChunhua Liang and Kefan Yi contributed equally to this work.
Abstract
Resveratrol (RES) has various pharmacological bioactivities and its anticancer effects in lung cancer have been proven. However, the underlying mechanisms of action of RES in lung cancer remain unclear. This study focused on Nrf2-mediated antioxidant systems in RES-treated lung cancer cells. A549 and H1299 cells were treated with various concentrations of RES at different times. RES decreased cell viability, inhibited cell proliferation, and increased the number of senescent and apoptotic cells in a concentration- and time-dependent manner. Moreover, RES-induced lung cancer cell arrest at the G1 phase was accompanied by changes in apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3). Furthermore, RES induced a senescent phenotype along with changes in senescence-related markers (senescence-associated β-galactosidase activity, p21, and p-γH2AX). More importantly, with prolonged exposure time and increased exposure concentration, intracellular reactive oxygen species (ROS) continuously accumulated, resulting in a decrease in Nrf2 and its downstream antioxidant response elements, including CAT, HO-1, NQO1, and SOD1. Meanwhile, RES-induced ROS accumulation and cell apoptosis were reversed by N-acetyl-l-cysteine treatment. Taken together, these results suggest that RES disturb lung cancer cellular homeostasis by destroying the intracellular antioxidant pool to increase ROS production. Our findings provide a new perspective on RES intervention in lung cancer.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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