Background: The Myosin Phosphatase (MP) holoenzyme is composed of a Protein Phosphatase type 1
(PP1) catalytic subunit and a regulatory subunit termed Myosin Phosphatase Target subunit 1 (MYPT1). Besides
dephosphorylation of myosin, MP has been implicated in the control of cell proliferation via dephosphorylation
and activation of the tumor suppressor gene products, retinoblastoma protein (pRb) and merlin. Inhibition
of MP was shown to attenuate the drug-induced cell death of leukemic cells by chemotherapeutic agents, while
activation of MP might have a sensitizing effect.
Objective: Recently, Epigallocatechin-Gallate (EGCG), a major component of green tea, was shown to activate
MP by inducing the dephosphorylation of MYPT1 at phospho-Thr696 (MYPT1pT696
), which might confer enhanced
chemosensitivity to cancer cells.
Methods: THP-1 leukemic cells were treated with EGCG and Daunorubicin (DNR) and cell viability was analyzed.
Phosphorylation of tumor suppressor proteins was detected by Western blotting.
Results: EGCG or DNR (at sub-lethal doses) alone had moderate effects on cell viability, while the combined
treatment caused a significant decrease in the number of viable cells by enhancing apoptosis and decreasing
proliferation. EGCG plus DNR decreased the phosphorylation level of MYPT1pT696
, which was accompanied by
prominent dephosphorylation of pRb. In addition, significant dephosphorylation of merlin was observed when
EGCG and DNR were applied together.
Conclusion: Our results suggest that EGCG-induced activation of MP might have a regulatory function in mediating
the chemosensitivity of leukemic cells via dephosphorylation of tumor suppressor proteins.