Antitumor activity and toxicity relationship of annonaceous acetogenins in mice

CHEN Yong; CHEN Jianwei; WANG Yu; XU Shasha; WANG Siliang; LI Xiang

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Antitumor activity and toxicity relationship of annonaceous acetogenins in mice

CHEN Yong,CHEN Jianwei,WANG Yu,XU Shasha,WANG Siliang,LI Xiang * #

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210046

*Correspondence author

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Funding: Doctoral Fund of Ministry of Education of China （No.20113237110009), Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica）

Opened online:28 May 2012

Accepted by: none

Citation: CHEN Yong,CHEN Jianwei,WANG Yu.Antitumor activity and toxicity relationship of annonaceous acetogenins in mice[OL]. [28 May 2012] http://en.paper.edu.cn/en_releasepaper/content/4479256

Annonaceous acetogenins (ACGs) are one of the most interesting classes of natural products appearing in the past two decades. Here, we studied the antitumor activity and toxicity relationship of ACGs covering the three major structural classes of mono-tetrahydrofuran (THF), adjacent bis-THF and nonadjacent bis-THF compounds including annosquamin B (1), bullatacin (2) and Annosquatin B (3) in vivo. A single intraperitoneal (i.p.) injections of 100 μg/kg of 1-3 did not cause side effects in normal mice. Five doses of 25 and 50 μg/kg of 2 to H22 hepatoma cells xenografts bearing mice resulted in a above 61% reduction in tumor growth with no pathological changes, but hematologic parameters increased significantly in normal mice. Ten doses of 25, 50 and 100 μg/kg of 1 and 3 to the H22 hepatoma cells transplantation tumor model mice resulted in a maximum 53.7% and 58.7% reduction in tumor growth, respectively, and did not cause severe side effects in normal mice. This study provided the evidence that adjacent bis-THF ACGs showed higher antitumor activity, and also exhibited higher toxicity than mono-THF and nonadjacent bis-THF ACGs in vivo.

Keywords:Chemistry of Chinese Medicine; Annonaceous acetogenin; Antitumor; Toxicity; In vivo; Xenograft

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