Cancer therapy combination: green tea and a phosphodiesterase 5 inhibitor?

Abstract

The major constituent of green tea, (-)-epigallocatechin-3-O-gallate (EGCG), has been shown to have cancer-preventive and therapeutic activities. Numerous molecular targets for EGCG have been proposed, but the mechanisms of its anticancer activities are not clearly understood. In this issue of the JCI, Kumazoe et al. report that EGCG activates 67-kDa laminin receptor (67LR), elevates cGMP levels, and induces cancer cell apoptosis. Furthermore, a phosphodiesterase 5 inhibitor, vardenafil, synergizes with EGCG to induce cancer cell death. This is a provocative observation with important implications for cancer therapy. It also raises several issues for further investigation, such as the mechanism by which EGCG specifically activates 67LR.

Figure 1. Proposed mechanisms of anticancer action of EGCG.

The mechanism by which EGCG exerts its antitumor actions is unknown, but may involve one or more of the actions illustrated. EGCG can act as an antioxidant, reducing ROS and inhibiting cancer development, and paradoxically may promote the production of ROS in cancer cells and induce apoptosis. EGCG is also known to bind and modulate the activities of enzymes, receptors, and signaling molecules that affect cell growth and proliferation. Activation of 67LR by EGCG and inhibition of PDE5 activity by its inhibitors synergistically induce cancer cell apoptosis (8). DNMT1, DNA, methyltransferase 1; DHFr, dihydrofolate reductase; HGFR, HGF receptor; Bcl-2, B cell CLL/lymphoma 2; GRP78, glucose-regulated protein 78 kDa; Pin1, peptidyl cis/trans isomerase.