Triptolide Mediated Amelioration of Breast Cancer via Modulation of Molecular Pathways

Triptolide is the main bioactive molecule isolated from a root extract of Tripterigium wilfordii Hook F. of Celastraceae family. Chemically, it is a diterpenoid triepoxide molecule and its chemical formula is C₂₀H₂₄O₆. Its five-membered unsaturated lactone ring (D-ring) is crucial for anti-tumor potential and carbonyl group at C-18 position is essential to exert important influence on the interaction between triptolide and the targeted protein(s). It is bio-synthesized from deoxy-D-xylullose-5-phosphate (DOXP) pathway in the cell. Triptolide can induce apoptosis in a number of breast cancer cells by up-regulating different pro-apoptotic and down-regulating different anti-apoptotic molecules. In vitro experiments indicate that it can down regulate several cell cycle related genes and induces S-phase cell cycle arrest. Triptolide treatment can also modulate the expression of different cell signaling molecules, e.g. ERK, NF-κB, FAK, VEGF, β-catenin, AKT etc. In vivo experiments indicate that triptolide can effectively reduce breast tumor growth in the mouse model. Apart from the single drug treatment, triptolide can effectively be applied in combination therapy. Application of Triptolide with other chemotherapeutic drugs, very efficiently check the proliferation of tumor cells which reduces the effective concentration of the commercially available drugs thus reducing their toxic sideeffects. Although triptolide is very effective against a number of diseases, its higher degree of multi-organ toxicity limits its use of further clinical trial. Therefore, to reduce the toxic effects, a number of strategies have been developed which increase its water solubility and at the same time decrease the toxic effect. In this review article, we have addressed how triptolide participates in the antitumor processes in breast cancer cells.