Honokiol induces endoplasmic reticulum stress-mediated apoptosis in human lung cancer cells

• Published in: Life sciences (1973) Vol. 221; pp. 204 - 211
• Main Authors: Zhu, Jianfei, Xu, Shuonan, Gao, Wenli, Feng, Jianyu, Zhao, Guolong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.03.2019; Elsevier BV
• Subjects: A549 Cells; Anticancer properties; Antitumor activity; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; Biphenyl; Biphenyl Compounds - metabolism; Biphenyl Compounds - pharmacology; Cancer; Caspase; Caspase-9; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Survival - drug effects; Cell viability; Cholecystokinin; Colorectal carcinoma; Delta cells; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; ER stress; Honokiol; Humans; Leukemia; Lignans - metabolism; Lignans - pharmacology; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Melanoma; Natural products; Prostate cancer; Proteins; RNA, Small Interfering; Signal Transduction; Signaling; siRNA; Stress; Time dependence; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism; Wound healing; Honokiol; ER stress; Lung cancer; Apoptosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.01.046

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. 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. 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. 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.