Yoshihiro Uesawa1, Hiroshi Sakagami2, Noriyuki Okudaira3, Kazuhiro Toda4, Koichi Takao4, Hajime Kagaya5, Yoshiaki Sugita4. 1. Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan uesawa@my-pharm.ac.jp. 2. Meikai University Research Institute of Odontology (M-RIO), Mekai University School of Dentistry, Tokyo, Japan. 3. Division of Pharmacology, Mekai University School of Dentistry, Tokyo, Japan. 4. Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Japan. 5. Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
Abstract
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 [9] 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. Copyright
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 [9] 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. Copyright