Activation of p53/miR-34a tumor suppressor axis by Chinese herbal formula JP-1 in A549 lung adenocarcinoma cells

Chih Jung Yao, Jyh Ming Chow, Pei Chun Lin, Tsai Shu Hu, Hui Ching Kuo, Jhy Shrian Huang, Kuan Jen Bai, Gi Ming Lai

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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 activatesAMPK and reducesmTOR 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.

Original languageEnglish
Article number5989681
JournalEvidence-based Complementary and Alternative Medicine
Volume2016
DOIs
Publication statusPublished - 2016

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ASJC Scopus subject areas

  • Complementary and alternative medicine

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