Anti-tumor activity and immunological modification of ribosome-inactivating protein (RIP) from Momordica charantia by covalent attachment of polyethylene glycol.
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 NAsp- 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.
Li
Mengen
M
Key Laboratory of Bio-resources and Eco-environment Ministry of Education, College of Life Science of Sichuan University, Chengdu 610064, China.
Chen
Yiwen
Y
Liu
Zhongyu
Z
Shen
Fubing
F
Bian
Xiaoxiao
X
Meng
Yanfa
Y
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D029777:Momordica charantia / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D054788:Ribosome Inactivating Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012639:Seeds / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D010936:Plant Extracts; D011092:Polyethylene Glycols; D054788:Ribosome Inactivating Proteins