Targeting PML-RARα and oncogenic signaling pathways by Chinese herbal mixture Tien-Hsien liquid in acute promyelocytic leukemia NB4 cells

Tung-Iuan Lai, Chih Jung Yao, Chia Ming Yang, Shuang En Chuang, Jiann Long Yan, Chun Yen Liu, Suz Wen Chen, Kun Huang Yan, Gi Ming Lai

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Abstract

Tien-Hsien Liquid (THL) is a Chinese herbal mixture that has been used worldwide as complementary treatment for cancer patients in the past decade. Recently, THL has been shown to induce apoptosis in various types of solid tumor cells in vitro. However, the underlying molecular mechanisms have not yet been well elucidated. In this study, we explored the effects of THL on acute promyelocytic leukemia (APL) NB4 cells, which could be effectively treated by some traditional Chinese remedies containing arsenic trioxide. The results showed THL could induce G2/M arrest and apoptosis in NB4 cells. Accordingly, the decrease of cyclin A and B1 were observed in THL-treated cells. The THL-induced apoptosis was accompanied with caspase-3 activation and decrease of PML-RAR fusion protein. Moreover, DNA methyltransferase 1 and oncogenic signaling pathways such as Akt/mTOR, Stat3 and ERK were also down-regulated by THL. By using ethyl acetate extraction and silica gel chromatography, an active fraction of THL named as EAS5 was isolated. At about 0.5-1% of the dose of THL, EAS5 appeared to have most of THL-induced multiple molecular targeting effects in NB4 cells. Based on the findings of these multi-targeting effects, THL might be regarding as a complementary and alternative therapeutic agent for refractory APL.

Original languageEnglish
Article number984154
JournalEvidence-based Complementary and Alternative Medicine
Volume2011
DOIs
Publication statusPublished - 2011

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Acute Promyelocytic Leukemia
Apoptosis
tien-hsien liquid
Cyclin B1
Cyclin A
Silica Gel
Methyltransferases
Caspase 3
Gel Chromatography
Neoplasms

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Targeting PML-RARα and oncogenic signaling pathways by Chinese herbal mixture Tien-Hsien liquid in acute promyelocytic leukemia NB4 cells. / Lai, Tung-Iuan; Yao, Chih Jung; Yang, Chia Ming; Chuang, Shuang En; Yan, Jiann Long; Liu, Chun Yen; Chen, Suz Wen; Yan, Kun Huang; Lai, Gi Ming.

In: Evidence-based Complementary and Alternative Medicine, Vol. 2011, 984154, 2011.

Research output: Contribution to journalArticle

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AU - Lai, Tung-Iuan

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AU - Yang, Chia Ming

AU - Chuang, Shuang En

AU - Yan, Jiann Long

AU - Liu, Chun Yen

AU - Chen, Suz Wen

AU - Yan, Kun Huang

AU - Lai, Gi Ming

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