Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule-targeting agents by blocking cytokinesis.

Kinesin family member 20B (KIF20B, also known as MPHOSPH1) is a kinesin protein that plays a critical role in cytokinesis. Previously, we and others have demonstrated the oncogenic role of KIF20B in several cancers; however, the exact mechanisms underlying its tumorigenic effects remain unclear. Herein, we showed overexpression of KIF20B in human hepatocellular carcinoma (HCC) and reported a negative correlation between KIF20B level and prognosis of patients. Mechanistically, reducing KIF20B blockades mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent way. Importantly, reducing KIF20B acts synergistically with three microtubule-associated agents (MTA) to p53- or p14ARF-dependently suppress p53-wt or p53-null HCC cells. In addition to taxol, reducing KIF20B also enhanced the toxicity of two chemotherapeutic drugs, hydroxycamptothecin and mitomycin C. In conclusion, we found a novel mechanism in that blocking cytokinesis by KIF20B inhibition increases the efficacy of MTA; our results thus suggested a dual-mitotic suppression approach against HCC by combining MTA with KIF20B inhibition, which simultaneously blocks mitosis at both metaphase and telophase.

Reducing protein regulator of cytokinesis 1 as a prospective therapy for hepatocellular carcinoma.

Proteins that bind to microtubule are important for cell cycle, and some of these proteins show oncogenic characteristics with mechanisms not fully understood. Herein we demonstrate overexpression of protein regulator of cytokinesis 1 (PRC1), a microtubule-associated regulator of mitosis, in human hepatocellular carcinoma (HCC). Moreover, upregulated PRC1 is associated with lower survival rates of HCC patients. Mechanistically, reducing PRC1 blocks mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent manner, and acts synergistically with microtubule-associated agents (MTAs) to suppress p53-wt or p53-null HCC cells in a p53- or p14ARF-dependent manner; while overexpressing PRC1 increases the resistance of HCC to taxol. A combined treatment of taxol/shPRC1 results in 90% suppression of tumor growth in subcutaneous HCC xenograft models. In orthotopic xenograft mice, reducing PRC1 significantly alleviates HCC development and hepatic injury. Together, our results suggest a dual-mitotic suppression approach against HCC by combining MTAs with cytokinesis inhibition, which blocks mitosis at both metaphase and telophase.

The bis(p-sulfonatophenyl)phenylphosphine-assisted synthesis and phase transfer of ultrafine gold nanoclusters.

Gold nanoclusters (Au NCs) have attracted intensive attention for their molecular-like properties such as luminescence and unique charging behavior. A facile route has been developed for the preparation of ultrafine Au NCs at room temperature. Bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium was used to stabilize the Au NCs obtained by NaBH(4) reduction of HAuCl(4) at pH of ∼12 and facilitated the phase transfer of Au NCs from aqueous phase to an organic medium based on electrostatic interaction. From the analyses of TEM, HRTEM, and XRD patterns, the formation of fcc structured Au NCs dominated by {200} facets was identified. The Au NCs transferred into toluene could be used as seeds for the formation of core-shell Au@Ag(2)S nanoparticles, providing for a promising strategy for the metal doping in semiconductor nanocrystals.