5,7-Dimethoxyflavone Augments Oolonghomobisflavan B-Mediated Apoptotic Cell Death in Multiple Myeloma Cells through Activation of the 67LR/cGMP/ASM Signaling Axis

Oolonghomobisflavan B (OHBFB) is a prominent and specific polyphenolic constituent of oolong tea. We previously identified a cell membrane receptor for OHBFB and showed that it induces cancer-selective cell death in vitro and in vivo, although its standalone anticancer efficacy is limited. 5,7-Dimethoxyflavone (5,7-DMF), a principal bioactive component of black ginger (Kaempferia parviflora), also exhibits anticancer activity. Here, we demonstrate that 5,7-DMF synergistically enhances the anticancer effect of OHBFB in multiple myeloma cells by boosting OHBFB-induced intracellular cyclic guanosine monophosphate (cGMP) production. Moreover, co-treatment with OHBFB and 5,7-DMF triggers apoptotic cell death in multiple myeloma cells, accompanied by activation of the cGMP/acid sphingomyelinase (ASM) pathway. In summary, 5,7-DMF amplifies the anticancer activity of OHBFB by upregulating cGMP in multiple myeloma cells.