Molecular cloning and anti-invasive activity of cathepsin L propeptide-like protein from Calotropis procera R. Br. against cancer cells

Journal of Enzyme Inhibition and Medicinal Chemistry

Chang Woo Kwon¹  SuBin Yeo¹  Hee Yang¹  Kyung-Min Park¹  Ki Won Lee¹  Pahn-Shick Chang²  Sang-Kyu Ye³  Ae Jin Jeong³ 

[1] Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea;Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea;Center for Food and Bioconvergence, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Kore;Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea;

关键词: Calotropis procera;    cysteine protease;    cathepsin L;    propeptide;    cancer cell invasion;   

DOI  :  10.1080/14756366.2018.1444609

来源: publisher

【 摘 要 】

Cathepsin L of cancer cells has been shown to play an important role in degradation of extracellular matrix for metastasis. In order to reduce cell invasion, cathepsin L propeptide-like proteins which are classified as the I29 family in the MEROPS peptidase database were characterized from Calotropis procera R. Br., rich in cysteine protease. Of 19 candidates, the cloned and expressed recombinant SnuCalCp03-propeptide (rSnuCalCp03-propeptide) showed a low nanomolar Ki value of 2.3 ± 0.2 nM against cathepsin L. A significant inhibition of tumor cell invasion was observed with H1975, HT29, MDA-BM-231, PANC1, and PC3 with a 76, 67, 67, 63, and 79% reduction, respectively, in invasion observed in the presence of 400 nM of the rSnuCalCp03-propeptide. In addition, thermal and pH study showed rSnuCalCp03-propeptide consisting of secondary structures was stable at a broad range of temperatures (30–70 °C) and pH (2–10, except for 5 which is close to the isoelectric point of 5.2).

【 授权许可】

CC BY