Since more than 75% of breast cancers overexpress estrogen receptors (ER), endocrine therapy targeting ER has significantly improved the survival rate. Nonetheless, breast cancer still afflicts women worldwide and the major problem behind it is resistance to endocrine therapy. We have previously shown the involvement of nuclear factor-κB (NF-κB) in neoplastic proliferation of human breast cancer cells; however, the association with the transformation of ER-positive cells remains unclear. In the current study, we focused on roles of NF-κB in the hormone dependency of breast cancers by means of ER-positive MCF-7 cells. Blocking of NF-κB signals in ER-negative cells stopped proliferation by downregulation of D-type cyclins. In contrast, the MCF-7 cells were resistant to NF-κB inhibition. Under estrogen-free conditions, the ER levels were reduced when compared with the original MCF-7 cells and the established cell subline exhibited tamoxifen resistance. Additionally, NF-κB participated in cell growth instead of the estrogen-ER axis in the subline and consequently, interfering with the NF-κB signals induced additive anticancer effects with tamoxifen. MMP-9 production responsible for cell migration, as well as the cell expansion in vivo, were suppressed by NF-κB inhibition. Therefore, we suggest that NF-κB is a master switch in both ER-positive and ER-negative breast cancers.
The chondroprotective effect of olive leaf extract (OLE) on knee osteoarthritis (OA) was studied with STR/ort mice (n = 5). OLE was administrated with a dosage of 100 mg/kg for 8 weeks and the OA severity score of hind limb knee joints was then measured. The Mankin scores of the knee joints of the non-OA control group, OA control group and OLE-treated group were 3.50, 11.13 and 7.20, respectively. This suggests that oral OLE supplements help prevent cartilage degeneration in STR/ort mice. In vitro, the synthesis of high molecular weight hyaluronan in synovial cells (HIG-82) was increased by OLE stimulation. This suggests that OLE modulates hyaluronan metabolism in synovial cells and improves OA symptoms. Our findings indicate that OLE intake inhibits cartilage destruction by increasing high molecular weight hyaluronan and thus preventing OA progress.
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