Reference - Detail
|Author||Uesawa Y, Sakagami H, Okudaira N, Toda K, Takao K, Kagaya H, Sugita Y.|
|Title||Quantitative Structure-Cytotoxicity Relationship of Cinnamic Acid Phenetyl Esters.|
BACKGROUND/AIM:Many phenolic acid phenethyl esters possess diverse biological effects including antioxidant, cytoprotective, anti-inflammation and anti-tumor activities. However, most previous antitumor studies have not considered the cytotoxicity against normal cells. Ten cinnamic acid phenetyl esters were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity and tumor-specificity, in order to find their new biological activities.
MATERIALS AND METHODS:Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by CC50 against tumor cells. Apoptosis markers were detected by western blot analysis. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization.
RESULTS:Western blot analysis demonstrated that  stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. QSAR analysis demonstrated that TS values were correlated with shape, size and ionization potential.
CONCLUSION:Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs.
|MeSH||Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / pathology Cell Line, Tumor Child Cinnamates / chemistry Cinnamates / pharmacology* Cinnamates / toxicity Esters / chemistry Esters / pharmacology* Esters / toxicity Fibroblasts / drug effects Head and Neck Neoplasms / drug therapy Head and Neck Neoplasms / pathology Humans Male Mouth Neoplasms / drug therapy Mouth Neoplasms / pathology Phenylethyl Alcohol / chemistry Phenylethyl Alcohol / pharmacology* Phenylethyl Alcohol / toxicity Quantitative Structure-Activity Relationship Squamous Cell Carcinoma of Head and Neck|
|Human and Animal Cells||Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902)|