Background: Multiple myeloma (MM) is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results: In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions: Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma.

Background: To investigate the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy on brain glucose metabolism in patients with diffuse large B cell lymphoma (DLBCL). Methods: Seventy-two patients with newly diagnosed DLBCL underwent FDG PET/CT brain and whole-body scans at baseline (PET0), in the interim of chemotherapy (PET2), and at the end (PET6) of chemotherapy. All three brain scans of each patient were analyzed using statistical parametric mapping software. Results: Compared with the PET0 scan, the PET2 and PET6 scans revealed a significantly higher glucose metabolism throughout the whole brain, with the PET6 scan revealing a higher metabolism than the PET2 scan. Patients with a complete response (CR) displayed decreased glucose metabolism in the lingual gyrus and increased glucose metabolism in the pons after chemotherapy compared with the findings in patients with partial responses or progressive disease. Conclusions: Brain glucose metabolism was affected by R-CHOP treatment throughout the entire chemotherapy protocol.