Background and Purpose
Epigallocatechin‐3‐gallate (EGCG) is a component of green tea known to have chemo‐preventative effects on several cancers. However, EGCG has limited clinical application, which necessitates the development of a more effective EGCG prodrug as an anticancer agent.
Experimental Approach
Derivatives of EGCG were evaluated for their stability and anti‐tumour activity in human chronic myeloid leukaemia (CML) K562 and KBM5 cells.
Key Results
EGCG‐mono‐palmitate (EGCG‐MP) showed most prolonged stability compared with other EGCG derivatives. EGCG‐MP exerted greater cytotoxicity and apoptosis in K562 and KBM5 cells than the other EGCG derivatives. EGCG‐MP induced Src‐homology 2 domain‐containing tyrosine phosphatase 1 (SHP‐1) leading decreased oncogenic protein BCR‐ABL and STAT3 phosphorylation in CML cells, compared with treatment with EGCG. Furthermore, EGCG‐MP reduced phosphorylation of STAT3 and survival genes in K562 cells, compared with EGCG. Conversely, depletion of SHP‐1 or application of the tyrosine phosphatase inhibitor pervanadate blocked the ability of EGCG‐MP to suppress phosphorylation of BCR‐ABL and STAT3, and the expression of survival genes downstream of STAT3. In addition, EGCG‐MP treatment more effectively suppressed tumour growth in BALB/c athymic nude mice compared with untreated controls or EGCG treatment. Immunohistochemistry revealed increased caspase 3 and SHP‐1 activity and decreased phosphorylation of BCR‐ABL in the EGCG‐MP‐treated group relative to that in the EGCG‐treated group.
Conclusions and Implications
EGCG‐MP induced SHP‐1‐mediated inhibition of BCR‐ABL and STAT3 signalling in vitro and in vivo more effectively than EGCG. This derivative may be a potent chemotherapeutic agent for CML treatment.