Synthesis of [3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride and investigation on its anti tumor effects against BGC-823

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, 1H 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.

A series of ursolic acid derivatives (three novel compounds UA-1a, UA-1b and UA-2) by modification at the C-3 or/and C-28 positions were synthesized and their cytotoxicities against human cancer cell lines HepG2, HT-29, and BGC-823 were evaluated by MTT assay. Among the prepared derivatives, [3β-acetoxy-urs-12-en-28-oyl]-1-monoglyceride (UA-1a) exhibited the highest antiproliferation activity. Its anti tumor activity against human gastric carcinoma BGC-823 was reported both in vitro and in vivo. The results indicated that UA-1a triggered the death of BGC-823 cells by inducing apoptosis via the mitochondria pathway.Figure optionsDownload as PowerPoint slide