title: Synthesis of [3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride and investigation on its anti tumor effects against BGC-823.
abstract: Ursolic acid (UA) as the leader compound was designed to prepare a series of derivatives (three novel compounds UA-1a, UA-1b and UA-2) by modification at the C3 and C28 positions. Their chemical structures were confirmed by IR, (1)H NMR and MS. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823 and HT-29 by the MTT assay. The novel derivative UA-1a, [3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride showed significant anti-growth ability against the assayed cancer cell lines, particularly against BGC-823, while low cytotoxicity to human normal gastric cell line GES-1. Further investigation revealed that UA-1a could induce apoptotic events of the treated BGC-823 cells, such as comet-like DNA bend, sub-G0/G1 phase accumulation and phosphatidylserine externalization. The activity of Caspase-3 was found to be up-regulated, while the expression of Bcl-2 and Survivin were down-regulated in UA-1a treated cells. UA-1a might trigger the death of BGC-823 cells by inducing apoptosis via the mitochondria pathway. UA-1a exerted stronger ability than Taxol to retard tumor growth in nude mice without leaving apparent toxicity to the hosts. The experimental data suggested that UA-1a would have a therapeutic potential in the treatment of gastric cancer.
authors.affiliation: College of Chemistry & Chemical Engineering, Fuzhou University, Fuzhou, PR China.
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Bai
authors.forename: Fen-Ling
authors.initials: FL
authors.lastname: Chen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yu
authors.forename: Yun-Quan
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Li
authors.forename: Yang-Hao
authors.initials: YH
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D050178:Monoglycerides / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000077022:Survivin; D014315:Triterpenes / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: C561762:(3-acetoxy-urs-12-en-28-oyl)-1-monoglyceride; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D050178:Monoglycerides; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D014315:Triterpenes; D053148:Caspase 3