論文 - 詳細
| RRC ID | 63458 |
|---|---|
| 著者 | Fukushi S, Yoshino H, Yoshizawa A, Kashiwakura I. |
| タイトル | p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines. |
| ジャーナル | BMC Cancer |
| Abstract |
BACKGROUND: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. 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. METHODS:The 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. RESULTS:The 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. CONCLUSIONS:We 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. |
| 巻・号 | 16 |
| ページ | 521 |
| 公開日 | 2016-7-25 |
| DOI | 10.1186/s12885-016-2585-6 |
| PII | 10.1186/s12885-016-2585-6 |
| PMID | 27456853 |
| PMC | PMC4960859 |
| MeSH | Antineoplastic Agents / pharmacology* Apoptosis Carcinoma, Non-Small-Cell Lung / drug therapy* Cell Line, Tumor DNA Damage Drug Screening Assays, Antitumor G2 Phase Cell Cycle Checkpoints Heterocyclic Compounds / pharmacology Humans Lung Neoplasms / drug therapy* Signal Transduction Structure-Activity Relationship Tumor Suppressor Protein p53 / physiology* |
| IF | 3.15 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) WI-38(RCB0702) |