The Promoting Activity on Human Megakaryocytopoiesis and Thrombopoiesis by Liquid Crystal-Related Compounds

Abstract

The liquid crystal compounds have a common structure with the cell membrane, having both a hydrophilic and hydrophobic residue, thus suggesting an affinity to the cell membrane. However, little information regarding a biological effect by liquid crystal compounds has been reported. In order to view the biological potential of liquid crystal compounds, the present study evaluated the in vitro human hematopoietic promoting effects by 18 liquid crystal-related compounds. In particular, these compounds are evaluated regarding their potential for platelet production from mature megakaryocytes by the culturing of CD34 ؉ cells derived from normal human peripheral blood. Often, in the case of severe thrombocytopenia there is no choice but to perform a transfusion of platelet concentrates. Three of the tested compounds promoted megakacyocyte generation in the culture stimulated with thrombopoietin alone. In addition, two compounds led to a significant increase in CD42a؉ particles which seemed to be platelets. At the same time, interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), that were used as a positive control for in vitro megakaryocytopoiesis and thrombopoiesis, resulted in a dramatic increase in the total number of cells; however, their promoting activity on in vitro hematopoiesis was almost at a similar level with the compounds. These results suggest that some liquid crystal-related compounds have a promoting effect on human thrombopoiesis, and that these compounds act with a different mechanism from either IL-3 or GM-CSF since the compounds specifically stimulated thrombopoiesis. The liquid crystal compounds may therefore be useful to develop a new functional medicine or a medical application.

Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line

“…However, compound 9 did not affect the cell cycle distribution and these pathways, and the mechanism of cell growth suppression by compound 9 remains unclear. In our previous study, we showed the promoting activity of LCRCs on human megakaryocytopoiesis and thrombopoiesis [16]. The mechanisms between the previous and present studies seem to be different because each effective compound and dose was different.…”

“…Generally, the liquid crystal is synthesized from various precursors, such as a flexible chain, a rigid aromatic core, and hydrophobic and hydrophilic units. Our previous study showed that these precursors, namely liquid crystal-related compounds (LCRCs), exhibited a promoting activity on human megakaryocytopoiesis and thrombopoiesis [16]. However, the possible use of LCRCs as an antitumor drug remains unclear.…”

Arachidonic acid and Docosahexanoic acid enhance platelet formation from human apheresis-derived CD34+ cells

“…Serum-free medium Stem-pro (10639-011) and Dynal CD34 C Isolation kit (11301D) was purchased from Invitrogen. All human recombinant growth factors, such as TPO (300-18), SCF (300-07), IL-3(200-03), IL-6(200-06), and Flt-3 (300- 19) were purchased from Peprotech Inc. The 2 poly-unsaturated fatty acids arachidonic acid (AA (A3555)) and Docosahexanoic acid (DHA (D2534).)…”

“…TPO is the primary regulator of megakaryopoiesis [16][17] whereas SCF, FLT-3, IL-3, IL-6 and IL-11 act as secondary regulators. 18 In attempts to further increase the efficiency of in vitro production of MKs and platelets various investigators have used additives like liquid crystal related compounds, 19 nicotinamide (vitamin B3), 20 heparin, 21 proteoglycans, 22 prostaglandins like 15-deoxy-delta-PGJ2. 23 Some investigators have used extracellular adhesive proteins like fibrinogen, fibronectin and VWF 24 to enhance platelet production.…”

p53-independent structure-activity relationships of 3-ring mesogenic compounds’ activity as cytotoxic effects against human non-small cell lung cancer lines

“…Some studies have focused on the structural affinities of cell membranes for LCs and have assessed the application of LCs as drug-delivery systems [ 17 , 18 ]. In previous studies, we investigated the cytotoxicity of LC compounds and their precursors (mesogenic compounds) [ 19 – 23 ] and showed that some amphiphilic LC compounds, such as cyanobiphenyl derivatives with terminal hydroxyl moieties, moderately suppressed cell growth in the NSCLC cell line A549 [ 20 ]. Furthermore, an amphiphilic LC precursor with three aromatic rings dramatically suppressed cell growth and induced apoptosis in A549 cells, but it also showed low cyototoxicity in normal WI-38 fibroblast cells [ 22 ].…”