eCAM Advance Access first published online on November 6, 2009
This version published online on November 23, 2009
eCAM, doi:10.1093/ecam/nep165
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Targeting PML-RAR
and Oncogenic Signaling Pathways by Chinese Herbal Mixture Tien-Hsien Liquid in Acute Promyelocytic Leukemia NB4 Cells
1Cancer Center, Taipei Medical University-Wan Fang Hospital, 2Formosa Cancer Foundation, Taipei, 3National Institute of Cancer Research, National Health Research Institutes, Zhunan, 4Department of Life Science, National Tsing Hua University, Hsinchu, 5School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan and 6Department of Chinese Internal Medicine, China Medical University Hospital, Taichung, Taiwan
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.
Keywords: acute promyelocytic leukemia – Chinese herbal mixture – molecular targeting
*To whom correspondence should be addressed. For reprints and all correspondence: Gi-Ming Lai, MD, Associate Investigator, National Institute of Cancer Research, National Health Research Institutes; Associate Professor in Medicine, Taipei Medical University; Deputy Director, Cancer Center, Taipei Medical University-Wan Fang Hospital, No.111, Section 3, Hsing-Long Road, Taipei 116, Taiwan, ROC. Tel: +886-2-29307930 ext. 8130/8421; Fax: +886-2-2933-8583; E-mail: gminlai{at}nhri.org.tw Tung-Yuan Lai, MD, PhD, Associate Professor, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan, Department of Chinese Internal Medicine, China Medical University Hospital, Taichung, Taiwan. No.91, Hsueh-Shih Road, Taichung 404, Taiwan. Tel: +886-4-22053366 ext. 3212; Fax: +886-4-22065141; E-mail: idlai{at}mail.cmu.edu.tw
In the original published version, there was an error in the affiliation of author Tung-Yuan Lai
Received June 23, 2009; accepted September 15, 2009