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Current Signal Transduction Therapy

Editor-in-Chief

ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

Molecular Mechanism of Anti-tumor Effect by Triptolide in Hematological Malignancies

Author(s): Youping Wang and Yan Chen

Volume 8, Issue 1, 2013

Page: [84 - 90] Pages: 7

DOI: 10.2174/1574362411308010011

Price: $65

Abstract

Triptolide is the major active ingredient of extracts derived from the traditional Chinese Medicine tripterygium wilfordii Hook F. As a complex natural extract, triptolide has a broad range of biological target points and exhibits a variety of pharmacological effects including anti-inflammatory, immunosuppressive, antioxidant, and anti-infertility. In addition, considerable evidences show that triptolide holds dramatic anti-tumor activities manifested by antiproliferative and proapoptotic activities at low nanomolar concentration. In clinical trial, some clinical departments in China have used triptolide to treat leukemia without toxicity of heart, liver, kidney as well as gastrointestinal tract at therapeutic dose. The present review delineates the molecular mechanism of the anti-tumor activities of triptolide in hematological malignancies. Our research shows the extensive biological effects of triptolide are mediated by means of perturbing multiple signal pathways and molecular cascades including regulation of tumor cell survival pathway (Bcl-2, Mcl-1, XIAP, caspases, nuclear factor-kappaB ), blocking the progression of cell cycle (CDKs, cyclin D1, P21wap1/cip1 and P27kip1), epigenetic modulation of target genes via interaction with histone methyltransferases and demethylases (EZH2, SUV39H1, NSD1, SMYD3, LSD1, JMJD2B, RIZ1), as well as regulation of angiogenesis pathway (VEGF, VEGFR) in hematological malignancies.

Keywords: Triptolide, Molecular mechanism, Anti-tumor, Human hematological malignancies, TUMOR CELL SURVIVAL


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