Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line

Abstract

The aim of this study was to evaluate the biological activity and pharmacological activity of several amphiphilic liquid-crystalline compounds (LCs), i.e. phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit, to explore novel anti-cancer functions of the LCs. The anti-cancer properties of the LCs were investigated in A549 human lung cancer cells by assessing cell growth, cell cycle distribution, and cell signaling pathways using a flow cytometer and a Western blot analysis. In addition, the effect of LCs on the growth of WI-38 normal fibroblasts was examined. Consequently, the phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through G1 phase arrest in A549 cells. Further analyses using phenylpyrimidine derivatives and precursors of a cyanobiphenyl compound demonstrated the structure-activity relationships. One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts. As a result, a novel pharmacological function was hypothesized to be inherent in the structure of the LCs themselves, and the dependence of the tumor-specific activity on the hydrophobic group of phenylpyrimidine derivatives therefore remains an interesting issue. Our results suggest the possibility that the LCs themselves may act as a novel type of chemotherapeutic agent.

Suppressive effects of liquid crystal compounds on the growth of U937 human leukemic monocyte lymphoma cells

“…Compounds #5, #10, #12, and #13 had little effects against A549 cells and compound #8 induced not S-phase arrest observed present study but G1-phase arrest in A549 cells without apoptosis [8]. Nevertheless, apoptosis unrelated toxicity is common feature of compound #8, which is supporsed torelate with p53 independent mechanism because A549 and U937 cells have valid p53 genomic contexts [20,21].…”

“…The cytotoxic property and classes of active compound depend on cell types because compounds cytotoxic to U937 cells (#5, #8, #10-13) are not necessarily cytotoxic to other cell types, lung cancer A549 cells [8]. Compounds #5, #10, #12, and #13 had little effects against A549 cells and compound #8 induced not S-phase arrest observed present study but G1-phase arrest in A549 cells without apoptosis [8].…”

“…These results suggest that differences in the molecular structures of the LCs were responsible for the differences in their cell type-specific inhibitory effect. Previously, Takahashi et al demonstrated that the suppressive effects of cyanobiphenyl derivatives on A549 cells depended on alkyl chain length rather than on the terminal substrate or the position of hydroxyl moieties [8]. Interestingly, both compounds #8 and #13, which showed strong cytotoxic effects against U937 cells, possess -O(CH 2 ) 6 OH in their structure.…”

“…One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts [8,9]. However, it is not yet known whether these LCs have cytotoxic properties against non-solid type tumor leukemic cells that are commonly treated by chemotherapy.…”

Regulation of DNA damage response and cell cycle in radiation-resistant HL60 myeloid leukemia cells

“…Western blotting was performed as described in a previous report (11). Briefly, cells were treated with each compound in the medium and incubated for 24 h. Harvested cells were lysed with 50 mM HEPES-HCl (pH 7.4), 100 mM NaCl, 1% Triton X-100, and 1 mM phenylmethylsulfonyl fluoride (PMSF; Wako) on ice for 30 min and subjected to sonication twice for 30 sec at ice-cold temperature.…”