Aralin, a type II ribosome-inactivating protein from Aralia elata, exhibits selective anticancer activity through the processed form of a 110-kDa high-density lipoprotein-binding protein: a promising anticancer drug.

Abstract

Aralin from Aralia elata is a newly identified type II ribosome- inactivating protein, which preferentially induces apoptosis in cancer cells. In this study, we identified that the aralin receptor is a 110-kDa high-density lipoprotein-binding protein (HDLBP), which functions as a HDL receptor. The sensitivities of tumor cell lines to aralin were dependent on the expression levels of the 110-kDa HDLBP and its forced expression in aralin-resistant Huh7 cells conferred aralin sensitivity. HDLBP-knockdown HeLa cells showed a significant aralin resistance in vitro and in vivo. Conversely, ectopic expression of the 150-kDa HDLBP resulted in increased aralin sensitivity in vivo, accompanying enhanced expression of the 110-kDa HDLBP. Thus, these results showed that the 110-kDa HDLBP in lipid rafts acted as an aralin receptor and that its expression levels determined aralin sensitivity, suggesting that aralin could be a promising anticancer drug for HDLBP-overexpressing tumors.

• Authors: Hiroko Otsuka, Yoshitaka Gotoh, Takashi Komeno, Takahide Ono, Yasushi Kawasaki, Naoyuki Iida, Yoshio Shibagaki, Seisuke Hattori, Makoto Tomatsu, Hirotada Akiyama, Fumio Tashiro
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 453 Issue 1 Pg. 117-23 (Oct 10 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25261720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Lipoproteins, HDL
• RNA-Binding Proteins
• Receptors, Lipoprotein
• Recombinant Proteins
• Ribosome Inactivating Proteins, Type 2
• aralin
• high density lipoprotein receptors
• high density lipoprotein binding protein

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacokinetics, pharmacology)
• Aralia (chemistry)
• Cell Line, Tumor
• Gene Knockdown Techniques
• HeLa Cells
• Hep G2 Cells
• Humans
• Lipoproteins, HDL (antagonists & inhibitors, genetics, metabolism)
• Membrane Microdomains (metabolism)
• Mice, Nude
• Molecular Weight
• RNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• Receptors, Lipoprotein (antagonists & inhibitors, genetics, metabolism)
• Recombinant Proteins (genetics, metabolism)
• Ribosome Inactivating Proteins, Type 2 (chemistry, pharmacokinetics, pharmacology)
• Xenograft Model Antitumor Assays