Inhibition of Human MCF-7 Breast Cancer Cells and HT-29 Colon Cancer Cells by Rice-Produced Recombinant Human Insulin-Like Growth Binding Protein-3 (rhIGFBP-3): e77516

• Published in: PloS one 2013-10, Vol.8 (10)
• Main Authors: Cheung, Stanley CK, Long, Xiaohang, Liu, Lizhong, Liu, Qiaoquan, Lan, Linlin, Tong, Peter CY, Sun, Samuel SM
• Format: Article
• Language: English
• Subjects: Angiogenesis; Oryza sativa
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0077516

Background Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. Methodology/Principal Findings We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 plus or minus 1.72% vs 45.00 plus or minus 0.86%, p < 0.05; 50.84 plus or minus 1.97% vs 45.00 plus or minus 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 plus or minus 3.84% vs 18.01 plus or minus 13.81%, p < 0.05 and 54.7 plus or minus 9.44% vs 18.01 plus or minus 13.81%, p < 0.05 respectively) when compared with wild type rice. Conclusion/Significance These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.