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

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

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.
原文英語
文章編號5989681
期刊Evidence-based Complementary and Alternative Medicine
2016
DOIs
出版狀態已發佈 - 2016

指紋

Neoplasms
Apoptosis
Lung Neoplasms
Proteins
Epithelial-Mesenchymal Transition
Complementary Therapies
Drug Resistance
Cause of Death
Cell Cycle
Therapeutics
Cell Proliferation
Adenocarcinoma of lung
Neoplasm Metastasis
Recurrence
Growth

ASJC Scopus subject areas

  • Complementary and alternative medicine

引用此文

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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 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.",
author = "Yao, {Chih Jung} and Chow, {Jyh Ming} and Lin, {Pei Chun} and Hu, {Tsai Shu} and Kuo, {Hui Ching} and Huang, {Jhy Shrian} and Bai, {Kuan Jen} and Lai, {Gi Ming}",
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T1 - Activation of p53/miR-34a tumor suppressor axis by Chinese herbal formula JP-1 in A549 lung adenocarcinoma cells

AU - Yao, Chih Jung

AU - Chow, Jyh Ming

AU - Lin, Pei Chun

AU - Hu, Tsai Shu

AU - Kuo, Hui Ching

AU - Huang, Jhy Shrian

AU - Bai, Kuan Jen

AU - Lai, Gi Ming

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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