title: Activation of p53/miR-34a Tumor Suppressor Axis by Chinese Herbal Formula JP-1 in A549 Lung Adenocarcinoma Cells.
abstract: Lung cancer is the leading cause of cancer death worldwide; the most common pathologic type is lung adenocarcinoma (LADC). In spite of the recent progress in targeted therapy, most LADC patients eventually expired due to the inevitable recurrence and drug resistance. New complementary agent with evidence-based molecular mechanism is urgently needed. MiR-34a is an important p53 downstream tumor suppressor, which regulates apoptosis, cell-cycle, EMT (epithelial mesenchymal transition), and so forth. Its expression is deficient in many types of cancers including LADC. Here, we show that a Chinese herbal formula JP-1 activates p53/miR-34a axis in A549 human LADC cells (p53 wild-type). Treatment with JP-1 induces p53 and its downstream p21 and BAX proteins as well as the miR-34a, resulting in growth inhibition, colony formation reduction, migration repression, and apoptosis induction. Accordingly, the decreases of miR-34a downstream targets such as CDK6, SIRT1, c-Myc, survivin, Snail, and AXL were observed. Moreover, JP-1 activates AMPKαand reduces mTOR activity, implying its inhibitory effect on the energy-sensitive protein synthesis and cell proliferation signaling. Our results show that JP-1 activates p53/miR-34a tumor suppressor axis and decreases proteins related to proliferation, apoptosis resistance, and metastasis, suggesting its potential as a complementary medicine for LADC treatment.
authors.affiliation: Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; Comprehensive Cancer Center of Taipei Medical University, Taipei 11031, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chih-Jung
authors.identifier: 0000-0001-6072-4033
authors.initials: CJ
authors.lastname: Yao
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Chow
authors.affiliation: Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Tsai-Shu
authors.initials: TS
authors.lastname: Hu
authors.affiliation: Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Comprehensive Cancer Center of Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Jhy-Shrian
authors.initials: JS
authors.lastname: Huang
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Kuan-Jen
authors.identifier: 0000-0001-8291-4436
authors.initials: KJ
authors.lastname: Bai
authors.affiliation: Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; Comprehensive Cancer Center of Taipei Medical University, Taipei 11031, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Gi-Ming
authors.identifier: 0000-0001-6123-8870
authors.initials: GM
authors.lastname: Lai