title: Honokiol, a potential therapeutic agent, induces cell cycle arrest and program cell death in vitro and in vivo in human thyroid cancer cells.
abstract: Thyroid cancer is the most common endocrine malignancy, the global incidence rate of which is rapidly rising. Surgery and radioiodine therapies are common and effective treatments only for nonmetastasized primary tumors. Therefore, effective treatment modalities are imperative for patients with radioiodine-resistant thyroid cancer. Honokiol, a biophenolic compound derived from Magnolia spp., has been shown have diverse biological and pharmacological activities, including anti-inflammatory, antioxidative, antiangiogenic, and anticancer properties. In the present study, three human thyroid cancer cell lines, namely anaplastic, follicular, and poorly differentiated thyroid cancer cells, were used to evaluate the chemotherapeutic activity of honokiol. Cell viability, cell cycle, apoptosis, and autophagy induction were determined through flow cytometry and western blot analysis. We found that honokiol treatment can suppress cell growth, induce cell cycle arrest, and enhance the induction of caspase-dependent apoptosis and autophagy in cancer cells. Moreover, honokiol treatment modulated signaling pathways including Akt/mTOR, ERK, JNK, and p38 in the studied cells. In addition, the antitumorigenic activity of honokiol was also confirmed in vitro and in vivo. Our data provide evidence that honokiol has a unique application in chemotherapy for human thyroid cancers.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan; College of Nursing and Health Sciences, Dayeh University, Changhua, Taiwan.
authors.forename: Chieh-Hsiang
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
authors.forename: Shu-Hsin
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Lim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
authors.forename: Hui-I
authors.initials: HI
authors.lastname: Yu
authors.affiliation: Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan; Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan. Electronic address: yingray.lee@gmail.com.
authors.forename: Ying-Ray
authors.initials: YR
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Anti-cancer; Apoptosis; Autophagy; Honokiol; Thyroid cancer