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

Abstract

Liquid crystals are the state of matter existing between the liquid and the crystalline phase, and there is a recent surging interest in its biological effects. Our previous study showed that liquid crystal-related compounds (LCRCs), which are precursors of the liquid crystal, enhanced hematopoietic differentiation at a relatively low concentration (Biol Pharm Bull, 32, 2009). However, biological potentials of LCRCs on tumor cells are unclear. In this study, the biological activity of 16 LCRCs to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (compound 7) and 2-{4-(4-hexyloxyphenyl)phenyl}-5-hydroxypyrimidine (compound 9) showed marked growth suppression of K562 cells at μM range. These compounds are similar in structure with a core of three aromatic rings including a pyrimidine ring and residues of one alkyl chain and one hydroxide on either side. In addition, only compound 7 induced the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells. The contrasting results between compounds 7 and 9 indicate different mechanisms to suppress the cell proliferation between the two compounds. These results suggest the possibility of LCRCs for application as new antitumor drugs.

A liquid crystal-related compound induces cell cycle arrest at the G2/M phase and apoptosis in the A549 human non-small cell lung cancer cell line

“…In the present study, we demonstrated that LCRCs possessing three aromatic rings, whose potential to induce apoptosis had been previously demonstrated in human chronic myelogenous leukemia K562 cells (12), suppressed cell growth in human non-small cell lung cancer A549 cells ( Fig. 2A).…”

“…On the other hand, c-Jun N terminal kinase (JNK) is involved in not only apoptosis but also cell cycle arrest (19). Furthermore, since Fukushi et al reported that LCRC-1 activated JNK in the K562 cells (12), there is a possibility that JNK is associated with suppression of LCRC-1 in the A549 cells. However, a JNK inhibitor VIII (Calbiochem ® ) did not affect cell suppression by LCRC-1 in the A549 cells (data not shown).…”

“…We previously demonstrated that LCCs suppressed the cell growth of the non-small cell lung cancer (NSCLC) cell line A549 through G1-phase arrest, although it did not induce cell death (11). Recently, we also reported that some LCRCs dramatically suppressed cell growth and induced apoptosis in human chronic myelogenous leukemia K562 cells (12). Although leukemic cells are more sensitive to chemotherapy and ionizing radiation compared with solid malignancies (13), there is a possibility that these LCRCs potentially suppress cell growth and induce cell death in solid malignancies including NSCLC.…”

Liquid Crystals: A Novel Approach for Cancer Detection and Treatment

“…Following this interest, four compounds were evaluated for their anti-cancer function: 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (LC1), 2-{4-(4-hexyloxyphenyl)phenyl}-5-hydroxypyrimidine (LC2), 4′-[(6-hydroxyhexyl)oxy]-[1,1′-biphenyl]-4-carbonitrile (LC3), and 4-(4-(5-octylpyridin-2-yl)phenoxyl)butan-1-ol (LC4). These LCs showed marked cell growth suppression, cell cycle arrest at the G2/M phase, and apoptosis [ 121 , 129 , 130 , 131 , 132 , 133 , 134 ]. Chronic myelogenous leukemia K562 cells, A549 human lung cancer cells, and U937 human leukemic monocyte lymphoma cells were used to test LCs anti-cancer properties by evaluating cell growth, cell cycle distribution, and signaling pathways using flow cytometry and Western blot analysis.…”

“…Both LC1 and LC2 showed cell growth suppression in K562 cells at a treatment in the µM range. The suppressive effects can be related to the specific chemical structures of LC1 and LC2 [ 133 ]. LC1 and LC2 both consist of a core of three aromatic rings (pyrimidine ring with one alkyl chain and one hydroxide on either side).…”