Jianfei Zhu1, Shuonan Xu2, Wenli Gao3, Jianyu Feng4, Guolong Zhao5. 1. Department of Thoracic Surgery, Shaanxi Provincial People's Hospital, Xi'an 710068, China; The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068, China. 2. Department of Thoracic Surgery, Shaanxi Provincial People's Hospital, Xi'an 710068, China; The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068, China; The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, China. 3. Department of Gynaecology, The Northwest Women and Children Hospital, Xi'an 710061, China. 4. Department of Cardiovascular Surgery, Xijing Hospital of The Fourth Military Medical University, Xi'an 710032, China. 5. Department of Thoracic Surgery, Shaanxi Provincial People's Hospital, Xi'an 710068, China; The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068, China; Department of Cardiothoracic Surgery, The Northwest Women and Children Hospital, Xi'an 710061, China. Electronic address: zhaoguolong127@163.com.
Abstract
AIMS: Honokiol is a hydroxylated biphenyl natural product and displays potent antitumor activity against several cancers including prostate cancer, melanoma, leukemia, and colorectal cancer. The present study was to investigate the in vitro activity of honokiol against A549 and 95-D human lung cancer cells. MAIN METHODS: A549 and 95-D cells were used with honokiol treatment. Cell viability was determined by CCK-8 assay. The cell migration and apoptosis were evaluated by wound healing assay and TUNEL staining method respectively. The expressions of ER-related proteins were analyzed by western blot and the CHOP siRNA was used to downregulate the CHOP expression. KEY FINDINGS: The results demonstrated that treatment of A549 and 95-D cells with honokiol significantly reduced cell viability in a dose- and time-dependent manner. Furthermore, honokiol treatment decreased cell migration and enhanced cell apoptosis, which is accompanied by the upregulation of the expressions of ER stress-induced apoptotic signaling molecules such as GRP78, phosphorylated PERK, phosphorylated eIF2α, CHOP, Bcl-2, Bax, and cleaved Caspase 9. Honokiol treatment-induced increase of ER stress-related signaling molecules and apoptotic proteins in A549 and 95-D cells were reversed by CHOP siRNA. SIGNIFICANCE: Collectively, we conclude that ER stress may participate in the action of the anticancer activity of honokiol in A549 and 95-D cells and induction of ER stress-related apoptosis may represent a novel therapeutic intervention for human lung cancer.
AIMS: Honokiol is a hydroxylated biphenyl natural product and displays potent antitumor activity against several cancers including prostate cancer, melanoma, leukemia, and colorectal cancer. The present study was to investigate the in vitro activity of honokiol against A549 and 95-D humanlung cancer cells. MAIN METHODS: A549 and 95-D cells were used with honokiol treatment. Cell viability was determined by CCK-8 assay. The cell migration and apoptosis were evaluated by wound healing assay and TUNEL staining method respectively. The expressions of ER-related proteins were analyzed by western blot and the CHOP siRNA was used to downregulate the CHOP expression. KEY FINDINGS: The results demonstrated that treatment of A549 and 95-D cells with honokiol significantly reduced cell viability in a dose- and time-dependent manner. Furthermore, honokiol treatment decreased cell migration and enhanced cell apoptosis, which is accompanied by the upregulation of the expressions of ER stress-induced apoptotic signaling molecules such as GRP78, phosphorylated PERK, phosphorylated eIF2α, CHOP, Bcl-2, Bax, and cleaved Caspase 9. Honokiol treatment-induced increase of ER stress-related signaling molecules and apoptotic proteins in A549 and 95-D cells were reversed by CHOP siRNA. SIGNIFICANCE: Collectively, we conclude that ER stress may participate in the action of the anticancer activity of honokiol in A549 and 95-D cells and induction of ER stress-related apoptosis may represent a novel therapeutic intervention for humanlung cancer.