title: Inhibitory effects of p-dodecylaminophenol on the invasiveness of human fibrosarcoma cell line HT1080.
abstract: Cancer is a major cause of death, and the development of new anticancer drugs is urgently needed. Invasion and metastasis are the primary causes of death due to cancer rather than growth of the primary tumor. In the current study, we examined the anti-invasive effects of p-dodecylaminophenol (1), which was developed based on N-(4-hydroxyphenyl)retinamide (2), a synthetic amide of all-trans-retinoic acid (3). In HT1080 cells 1 inhibited growth, induced apoptosis and arrested the cell cycle in S phase in a dose-dependent manner. In addition, 1 significantly suppressed cell invasion, and the activity and mRNA expression of matrix metalloproteinase-9 (MMP-9). Furthermore, the expression of the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), which is a negative regulator of MMP-9, was increased by treatment with 1. These results suggest that 1 could be an effective anti-cancer agent that suppresses cell growth through apoptosis induction and cell cycle arrest, which also inhibits cell invasion by decreasing MMP-9 expression due to an increase in RECK. Compound 1 might be useful clinically as a new and potent anticancer agent that could overcome adverse side effects of the retinoids.
authors: Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. t-noriko@hoshi.ac.jp
authors: Noriko
authors: N
authors: Takahashi
authors: Kotaro
authors: K
authors: Takeda
authors: Masahiko
authors: M
authors: Imai
mesh_terms: D000627:Aminophenols / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D015394:Molecular Structure; D009361:Neoplasm Invasiveness
chemical_list: C587537:4-dodecylaminophenol; D000627:Aminophenols; D000970:Antineoplastic Agents
keywords: 1; 2; 3; BSA; Cancer; DMSO; EDTA; ERK; Invasion; MEK; Metastasis; N-(4-hydroxyphenyl)retinamide, fenretinide; PBS; PI3K; RT-PCR; Retinoid; SD; all-trans-retinoic acid; bovine serum albumin; dimethylsulfoxide; ethylenediaminetetraacetic acid; extracellular signal-regulated kinase; mitogen-activated protein kinase kinase; p-dodecylaminophenol, 4-(dodecylamino)phenol; phosphate-buffered saline (1.5mM KH(2)PO(4), 8.1mM Na(2)HPO(4), 136.9mM NaCl, pH 7.2); phosphatidylinositol 3-kinase; reverse transcription-polymerase chain reaction; standard deviation