Abstract
BackgroundWe recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as “mesogenic compounds”) in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure–activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells.MethodsThe pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed.ResultsThe 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1–C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound.ConclusionsWe showed the p53-indepdent structure–activity relationships of mesogenic compounds related to the cytotoxic effects. These structure–activity relationships will be helpful in the development of more effective and cancer-specific agents.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2585-6) contains supplementary material, which is available to authorized users.
Highlights
We recently demonstrated the cytotoxicity of liquid crystal precursors in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy
We demonstrated that the 3-ring structure with terminal alkyl and hydroxyl groups and the alkyl chain lengths are structurally important for the cytotoxic effects of mesogenic compounds against human NSCLC cells
When the dose–response effects of C1 and C2 were examined in A549 cells (Additional file 1: Figure S1), we found that the 50 % inhibitory concentrations (IC50) of these compounds were 1.9 ± 0.1 μM for C1 and 2.3 ± 0.2 μM for C2; the cytotoxic effects of these compounds saturated around 10 μM
Summary
We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as “mesogenic compounds”) in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. The loss of p53 function in lung cancers results in resistance to radiation and molecularly targeted drugs such as epidermal growth factor receptor inhibitors [10, 11]. This is at least in part due to the impairment of p53mediated apoptosis induction [12, 13]. Since p53 mutations are observed in 50 % of NSCLC [14] and contribute to their resistance to chemotherapy [15], drugs exerting anticancer effects independent of p53 are required for NSCLC treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
