Title:Molecular Mechanism of Anti-tumor Effect by Triptolide in Hematological Malignancies
Volume: 8
Issue: 1
Author(s): Youping Wang and Yan Chen
Affiliation:
Keywords:
Triptolide, Molecular mechanism, Anti-tumor, Human hematological malignancies, TUMOR CELL SURVIVAL
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.