title: Cassane-type diterpenes from Caesalpinia minax induce apoptosis in pituitary adenoma: structure-activity relationship, ER stress and Wnt/β-catenin pathways.
abstract: Plant-derived natural products have been the highly significant sources of novel antitumor agents. The cassane-type diterpenes of genus Caesalpinia have been reported to bear antiproliferative activities toward different types of cancer cells. In this study, we evaluated the antineoplasmic activities of 16 natural origin cassane-type diterpenes isolated from the CHCl3extract of the seeds of C. minax in pituitary adenomas cells and identified caesalpin G (CAG) showed the strongest cytotoxicity. Moreover, we further investigated the structure-activity relationship and molecular mechanism of these derivatives systematically. The results confirmed the unsaturated lactone-type ring, hydroxyl at C-7, and alkenyl at C-11 or C-14 functionality as critical for anticancer activity in this family of natural products. In addition, the mechanism experiments also demonstrated unfolded protein response and ER stress and Wnt/β-catenin pathway were involved in the CAG-induced apoptosis.
authors: a Zhongshan School of Medicine , Sun Yat-sen University , Guangzhou 510080 , China.|b Brain center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital , Shenzhen University 1st Affiliated Hospital , Shenzhen 518035 , China.
authors: Zong-Yang
authors: ZY
authors: Li
authors: b Brain center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital , Shenzhen University 1st Affiliated Hospital , Shenzhen 518035 , China.|c Clinical Medicine Department , Shantou University Medical College , Shantou 515041 , China.
authors: Qing-Zhong
authors: QZ
authors: Li
authors: d Institute of Medicinal Plant Development, Chinese Academy of Medical Science , Peking Union Medical College , Beijing 100193 , China.
authors: Guo-Xu
authors: GX
authors: Ma
authors: b Brain center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital , Shenzhen University 1st Affiliated Hospital , Shenzhen 518035 , China.
authors: Lei
authors: L
authors: Chen
authors: b Brain center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital , Shenzhen University 1st Affiliated Hospital , Shenzhen 518035 , China.
authors: Ce
authors: C
authors: Zhang
authors: b Brain center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital , Shenzhen University 1st Affiliated Hospital , Shenzhen 518035 , China.
authors: Bao-Dong
authors: BD
authors: Chen
authors: d Institute of Medicinal Plant Development, Chinese Academy of Medical Science , Peking Union Medical College , Beijing 100193 , China.
authors: Jun-Shan
authors: JS
authors: Yang
authors: a Zhongshan School of Medicine , Sun Yat-sen University , Guangzhou 510080 , China.|b Brain center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital , Shenzhen University 1st Affiliated Hospital , Shenzhen 518035 , China.
authors: Wei-Ping
authors: WP
authors: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D029911:Caesalpinia / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010911:Pituitary Neoplasms / Q000188:drug therapy; D012639:Seeds / Q000737:chemistry; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000187:drug effects; D051176:beta Catenin / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D051153:Wnt Proteins; D051176:beta Catenin; C000617332:caesalpin G
keywords: Pituitary adenomas; Wnt/β-catenin; caesalpin G; cassane-type derivatives; structure–activity relationship