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Acta Biochimica et Biophysica Sinica Advance Access originally published online on July 30, 2009
Acta Biochimica et Biophysica Sinica 2009 41(9):792-799; doi:10.1093/abbs/gmp068
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Anti-tumor activity and immunological modification of ribosome-inactivating protein (RIP) from Momordica charantia by covalent attachment of polyethylene glycol

Mengen Li1, Yiwen Chen1, Zhongyu Liu1, Fubing Shen2, Xiaoxiao Bian1 and Yanfa Meng1,*

1 Key Laboratory of Bio-resources and Eco-environment Ministry of Education, College of Life Science of Sichuan University, Chengdu 610064, China
2 Department of Laboratory Medicine, Chengdu Medical College, Chengdu 610083, China

* Correspondence address. Tel: +86-28-85471541; Fax: +86-28-85412571; E-mail: yfmeng0902{at}scu.edu.cn


  Abstract

Ribosome-inactivating proteins (RIPs) are a family of enzymes that depurinate rRNA and inhibit protein biosynthesis. Here we report the purification, apoptosis-inducing activity, and polyethylene glycol (PEG) modification of RIP from the bitter melon seeds. The protein has a homogenous N-terminal sequence of N-Asp-Val-Ser-Phe-Arg. Moreover, the RIP displayed strong apoptosis-inducing activity and suppressed cancer cell growth. This might be attributed to the activation of caspases-3. To make it available for in vivo application, the immunogenicity of RIP was reduced by chemical modification with 20 kDa (mPEG)2-Lys-NHS. The inhibition activity of both PEGylated and non-PEGylated RIP against cancer cells was much stronger than against normal cells, and the antigenicity of PEGylated RIP was reduced significantly. Our results suggested that the PEGylated RIP might be potentially developed as anti-cancer drug.

Keywords    apoptosis; bitter melon seed; PEGylation; ribosome-inactivating protein

Received: February 19, 2009; Accepted: May 8, 2009
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