Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for co-activation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.
γ-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying these effects were examined. The results indicated that a γ-tocotrienol concentration over 30 μM inhibited the growth of HeLa cells with a 50% inhibitory concentration (IC50) of 46.90 ± 3.50 μM at 24 h, and significantly down-regulated the expression of proliferative cell nuclear antigen (PCNA) and Ki-67. DNA flow cytometric analysis indicated that γ-tocotrienol arrested the cell cycle at G0/G1 phase and reduced the S phase in HeLa cells. γ-tocotrienol induced apoptosis of HeLa cells in a time- and dose-dependent manner. γ-tocotrienol-induced apoptosis in HeLa cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, release of cytochrome from mitochondria, activation of caspase-9 and caspase-3, and subsequent poly (ADP-ribose) polymerase (PARP) cleavage. These results suggested that γ-tocotrienol could significantly inhibit cell proliferation through G0/G1 cell cycle arrest, and induce apoptosis via the mitochondrial apoptotic pathway in human cervical cancer HeLa cells. Thus, our findings revealed that γ-tocotrienol may be considered as a potential agent for cervical cancer therapy.
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