ABSTRACT
Pseudolaric Acid B (PAB), diterpenoid isolated from the root bark of Pseudolarix kaempferi Gordon tree (Pinaceae), exhibits an anti-proliferative and apoptotic activity in various cancer cell lines but to date, the effects of PAB on head and neck cancer (HNC) cell lines remain to be elucidated. In this study, we showed that PAB significantly inhibited the viability and caspase-dependent apoptosis in HN22 cell line. PAB-induced apoptosis is through inducing death receptor 5 (DR5) together with the increase in the expression of cleaved caspase-8. It also inhibited the proliferations and induced apoptosis through DR5 in other three HNC cell lines (HSC3, Ca9.22, and HSC4). Extending our in vitro findings, we found that ethanol extract of Pseudolarix kaempferi (2.5 mg/kg/day) reduced tumor growth in a xenograft model bearing HN22 cell line without any change in body weight. DR5 were also found to be increased in tumors tissue of PAB-treated mice without any apparent histopathological changes in liver or kidney tissues. Taken together, PAB may be a potential lead compound for chemotherapeutic agents against head and neck cancer.
Subject(s)
Apoptosis/drug effects , Diterpenes/pharmacology , Head and Neck Neoplasms/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Disease Models, Animal , Diterpenes/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Mice , Molecular Structure , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Xenograft Model Antitumor AssaysABSTRACT
Stereoselective syntheses of (+/-)-epibatidine analogues 2, which contain the 8-azabicyclo [3.2.1]octane ring system, were achieved by using palladium-catalyzed cross-coupling reaction from 4 and the analgesic activity was tested by Mouse writhing antinociceptive assay.
