title: Honokiol Decreases Lung Cancer Metastasis through Inhibition of the STAT3 Signaling Pathway.
abstract: Lung cancer is the leading cause of cancer death in the United States. Metastasis to lymph nodes and distal organs, especially brain, leads to severe complications and death. Preventing lung cancer development and metastases is an important strategy to reduce lung cancer mortality. Honokiol (HNK), a natural compound present in the extracts of magnolia bark, has a favorable bioavailability profile and recently has been shown to readily cross the blood-brain barrier. In the current study, we evaluated the antimetastatic effects of HNK in both the lymph node and brain mouse models of lung tumor metastasis. We tested the efficacy of HNK in preventing 18 H2030-BrM3 cell (brain-seeking human lung tumor cells) migration to lymph node or brain. In an orthotopic mouse model, HNK significantly decreased lung tumor growth compared with the vehicle control group. HNK also significantly reduced the incidence of lymph node metastasis and the weight of mediastinal lymph nodes. In a brain metastasis model, HNK inhibits metastasis of lung cancer cells to the brain to approximately one third of that observed in control mice. We analyzed HNK's mechanism of action, which indicated that its effect is mediated primarily by inhibiting the STAT3 pathway. HNK specifically inhibits STAT3 phosphorylation irrespective of the mutation status of EGFR, and knockdown of STAT3 abrogated both the antiproliferative and the antimetastatic effects of HNK. These observations suggest that HNK could provide novel chemopreventive or therapeutic options for preventing both lung tumor progression and lung cancer metastasis. Cancer Prev Res; 10(2); 133-41. ©2016 AACR.
authors.affiliation: Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.|Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.|Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Yongik
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.|Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.|Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Donghai
authors.initials: D
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tina C
authors.initials: TC
authors.lastname: Wan
authors.affiliation: Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.|Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin. myou@mcw.edu.|Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D017705:Lignans; D050796:STAT3 Transcription Factor; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols