Hirofumi Tachibana

(−)‐Epigallocatechin‐3‐ O ‐gallate (EGCG) is one of the major components of green tea polyphenol. Previous studies have shown that EGCG induces cancer‐specific cell death in vitro and in vivo without causing severe side effects. However, the anti‐cancer effect of EGCG alone is limited. 5,7‐dimethoxyflavone (5,7‐DMF), one of the principal functional components of black ginger ( Kaempferia parviflora ), also exerts anti‐cancer effects. Here, we show that 5,7‐DMF synergistically enhances the anti‐cancer effect of EGCG in multiple myeloma cells by potentiating EGCG‐induced intracellular cyclic guanosine monophosphate (cGMP) production. Moreover, the combination of EGCG and 5,7‐DMF induces apoptotic cell death in multiple myeloma cells, and this is accompanied by activation of the cGMP/acid sphingomyelinase (ASM)/cleaved caspase‐3 pathway. In conclusion, we have shown that 5,7‐DMF enhances the anti‐cancer effect of EGCG by upregulating cGMP in multiple myeloma cells.