Targeting PML‐RARα and Oncogenic Signaling Pathways by Chinese Herbal Mixture Tien-Hsien Liquid in Acute Promyelocytic Leukemia NB4 Cells

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-RARα 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.

Ferulsinaic acid attenuation of advanced glycation end products extends the lifespan ofCaenorhabditis elegans

“…These herbal combinations are believed to act synergistically to harmonize beneficial effects and to neutralize or minimize the toxic or adverse effects of individual constituent herbs. Recently, numerous efforts have been made to investigate the mechanisms of action of Chinese herbal formulae using modern scientific methodology [3–5] . In‐vitro and in‐vivo studies on the individual herbs or constituents of classic formulae have been reported and many herbal medicines have immunomodulatory or antioxidant effects that may offer clinically relevant therapeutics for patients with disorders associated with ageing [6,7] …”

“…Recently, numerous efforts have been made to investigate the mechanisms of action of Chinese herbal formulae using modern scientific methodology. [3][4][5] In-vitro and in-vivo studies on the individual herbs or constituents of classic formulae have been reported and many herbal medicines have immunomodulatory or antioxidant effects that may offer clinically relevant therapeutics for patients with disorders associated with ageing. [6,7] The exclusively old-world genus Ferula, belonging to the family Apiaceae, has some 130 species distributed throughout the Mediterranean area and Central Asia.…”

Regulation of p21, MMP-1, and MDR-1 Expression in Human Colon Carcinoma HT29 Cells by Tian Xian Liquid, a Chinese Medicinal Formula, In Vitro and In Vivo

“…Previous experiments reported that TXL had inhibitory effects on different carcinomas. 3,4 However, the mechanisms of action of TXL on antiproliferation, antimetastasis, and reversion of MDR on HT29 colon cancer have not been reported so far.…”

Harnessing Traditional Chinese Medicine to Improve Cancer Therapy: Issues for Future Development

“…Yao et al tested an aqueous extract of THL in APL NB4 cells and found that the extract could cause cell cycle arrest and induce apoptosis [25]. An ethyl acetate/nhexane extract of THL, however, was found to be 100 times more potent than THL, suggesting that the active anticancer components in THL are relatively hydrophobic.…”