Low-density lipoprotein receptor-related protein 1 is an essential receptor for trichosanthin in 2 choriocarcinoma cell lines.
Type-I ribosome-inactivating protein-trichosanthin (TCS) exhibits selective cytotoxicity toward different types of cells. It is believed that the cytotoxicity results from the inhibition of ribosomes to decrease protein synthesis, thereby indicating that there are specific mechanisms for TCS entry into target cells to reach the ribosomes. Low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a large scavenger receptor that is responsible for the binding and endocytosis of diverse biological ligands on the cell surface. In this study, we demonstrated that 2 choriocarcinoma cell lines can significantly bind and internalize TCS. In contrast, Hela cell line displayed no obvious TCS binding and endocytosis. Furthermore LRP1 gene silencing in JAR and BeWo cell lines blocked TCS binding; TCS could also interact with LRP1.The results of our study established that LRP1 was a major receptor for phagocytosis of TCS in JAR and BeWo cell lines and might be the molecular basis of TCS abortificient and anti-choriocarcinoma activity.
Jiao
Yizu
Y
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Liu
Wangyi
W
D000020:Abortifacient Agents, Nonsteroidal / Q000378:metabolism* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism*; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D034741:RNA, Small Interfering / Q000235:genetics; D015978:Trichosanthin / Q000378:metabolism* / Q000494:pharmacology
D000020:Abortifacient Agents, Nonsteroidal; D000972:Antineoplastic Agents, Phytogenic; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D034741:RNA, Small Interfering; D015978:Trichosanthin