Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells.

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

Polygoni Rhizoma inhibits inflammatory response through inactivation of nuclear factor-kappaB and mitogen activated protein kinase signaling pathways in RAW264.7 mouse macrophage cells.

The objective of this study was to determine the antiinflammatory effects of Polygoni Rhizoma (PR), an Oriental medicinal herb, in interleukin 1 beta (IL-1ß) and lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage cells. PR significantly reduced the production of pro-inflammatory cytokines such as IL-6, tumor necrosis factor alpha (TNF-α) and pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) even at a concentration of 1 µg/mL in the cells. In addition, PR inhibited the transcriptional activity of NF-κB as well as the degradation and phosphorylation of inhibitory kappa B alpha (IκBα). Furthermore, PR suppressed the phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase 1/2 (JNK1/2) in IL-1ß and LPS-treated RAW264.7. The results suggest that PR exerts an antiinflammatory property by inhibiting iNOS, COX-2, TNF-α and IL-6 production in association with inactivation of the NF-κB and MAPK signaling pathways in RAW 264.7 cells.