Antitumor Effects And Mechanisms Of Curcumin On Human Multiple Myeloma Cell Lines

Objective Curcumin is a novel antitumor drug extracted from plant. Existing evidence suggested that curcumin could inhibit proliferation, induce apoptosis of several tumor cell lines, and it has synergetic effects with many chemotherapeutic drugs. Moreover no toxicity to normal tissues has been found. In this study, we observed the effects of Cur on proliferation and apoptosis of human multiple myeloma cell lines (RPMI8226 and H929). Synergetic effects of curcumin and adriamycin(Adr) was also studied. The purpose of this study is to provide experimental evidence for clinical application of curcumin in multiple myeloma.Methods The effect of curcumin on proliferation of RPMI8226 and H929 was observed with MTT assay. Synergetic effect of curcumin and Adr was analyzed by median-effect principle. Changes in cell morphology and ultrastructure after administration of curcumin were observed with electron microscope. Cell cycle distribution and apoptosis were studied with flow cytometry. Expression of survivin,bcl-2,bax mRNA was detected by RT-PCR.Results Curcumin could inhibit the proliferation of RPMI8226 and H929 cells in a time- and dose-dependent manner. The IC50 values for RPMI8226 and H929 cell line were 12.15μmol/L,17.24μmol/L respectively. The combination of curcumin and Adr showed synergistic effect even at low concentration of Adr. After treatment with 10μmol/L curcumin for 24h, treated cells showed significant morphological change such as nuclear condensation, karyopycnosis, nuclear fragmentation and apoptotic body. Apoptotic ratio of treated cells was significantly higher than untreated controls (36.9% vs 10.6%, p<0.05). Cells treated with curcumin showed cell cycle arrest at G2/M phase. Curcumin upregulated expression of survivin,bcl-2, while bax mRNA was significantly downregulated.Conclusions (1) Curcumin could inhibit the proliferation of multiple myeloma cells; (2) The combination of curcumin and Adr showed synergistic effect even at low concentration of Adr; (3) Curcumin could induce apoptosis of multiple myeloma cells,causing cell cycle arrest at G2/M phase; (4) Curcumin downregulates survivin,bcl-2 mRNA while upregulating bax mRNA.