Novel pyrrolidine-aminophenyl-1,4-naphthoquinones: structure-related mechanisms of leukemia cell death.

Novel derivatives of aminophenyl-1,4-naphthoquinones, in which a pyrrolidine group was added to the naphthoquinone ring, were synthesized and investigated for the mechanisms of leukemic cell killing. The novel compounds, TW-85 and TW-96, differ in the functional (methyl or hydroxyl) group at the para-position of the aminophenyl moiety. TW-85 and TW-96 were found to induce concentration- and time-dependent apoptotic and/or necrotic cell death in human U937 promonocytic leukemia cells but only TW-96 could also kill K562 chronic myeloid leukemia cells and CCRF-CEM lymphoblastic leukemia cells.

Induction of death of leukemia cells by TW-74, a novel derivative of chloro-naphthoquinone.

We have previously shown that a 2-chloro-1,4-naphthoquinone derivative (TW-92) induces cell death in leukemia cells. TW-92 exhibited relatively high selectivity towards primary Acute Myeloid Leukemia (AML) cells, as compared to normal mononuclear cells. In view of the selectivity of this family of naphthoquinones, novel chloroaminophenylnaphthoquinone isomers with different methyl substitutions on the phenyl ring were synthesized, and their effect on leukemia cells was tested.

Highly efficient osteogenic differentiation of human mesenchymal stem cells by eradication of STAT3 signaling.

Human bone marrow-derived mesenchymal stem cells (hMSCs) are promising candidates for cellular therapy owing to their multipotency to differentiate into several cell lineages. Elucidating the signaling events involved in the response of hMSCs to diverse stimulants affecting their differentiation may considerably promote their clinical use. In this study, we attempted to illuminate the molecular signaling networks involved in bone morphogenetic protein (BMP)-stimulated hMSC osteogenic differentiation.

The anti-leukaemic activity of novel synthetic naphthoquinones against acute myeloid leukaemia: induction of cell death via the triggering of multiple signalling pathways.

Naphthoquinones, such as menadione, display lower toxicity than anthracyclins used in cancer chemotherapy. Novel anti-leukaemic compounds comprised of chloro-amino-phenyl naphthoquinones with substitutions on the benzoic ring were developed. Structure-activity relationship studies indicated that the analogue with both methyl and amine substitutions (named TW-92) was the most efficient in killing leukaemic cells.

Signal transducer and activator of transcription 3-A key molecular switch for human mesenchymal stem cell proliferation.

Human bone marrow mesenchymal stem cells are multipotent cells with enormous potential for cellular therapies. Identifying those mediators that induce human bone marrow mesenchymal stem cell proliferation and elucidating the signaling networks involved will encourage clinical efforts exploiting such cells. Here, we demonstrate that platelet-derived growth factor-BB and basic fibroblast growth factor induce human bone marrow mesenchymal stem cell proliferation.

Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes cardiac tissue assembly.

Deciphering the cellular signals leading to cardiac muscle assembly is a major challenge in ex vivo tissue regeneration. For the first time, we demonstrate that pulsatile interstitial fluid flow in three-dimensional neonatal cardiac cell constructs can activate ERK1/2 sixfold, as compared to static-cultivated constructs. Activation of ERK1/2 was attained under physiological shear stress conditions, without activating the p38 cell death signal above its basic level.

The eyestalk-androgenic gland-testis endocrine axis in the crayfish Cherax quadricarinatus.

In decapod crustaceans, a number of neurohormones regulating a variety of physiological processes, including reproduction, are to be found in the X-organ-sinus gland complex of the eyestalk. Bilateral eyestalk ablation was thus performed in mature males of the Australian red claw crayfish Cherax quadricarinatus with the aim of studying the role of eyestalk-borne hormones on spermatogenic activity in the testis and on the androgenic gland (AG). The latter gland controls the differentiation and functioning of male sexual characteristics in crustaceans.