Research team led by Dr. Po-Huang Liang has identified a small-molecule inhibitor I-Lys, which can activate Caspase-7 to selectively kill cancer cells. Dr. Liang collaborated with the Genomics Research Center, Academia Sinica and two local hospitals using drug-resistant cancers cells and cancer cells that cause poor prognosis in cancer patients as subjects. The research results was published on-line by the Journal of Clinical Investigation on August 27, 2013 and selected as a special report by the journal.
Caspase-3 is a major executioner protein of proteolytic degradation during apoptosis. However, Caspase-3 down-regulation (CASP3/DR) occurs to enable cancer cells survive therapy-induced apoptosis. The structurally and functionally similar caspase-7 was found to maintain cellular homeostasis in cancer cells. Thus, the research team synthesised I-Lys to selectively bind to Caspase-7 in order to disrupt the protein-protein interaction with its inhibitor XIAP(X-linked inhibitor of apoptosis protein) to release Caspase-7 and execute apoptosis only in cancer cells.
From clinical samples, CASP3/DR and Caspase-7 accumulation have been found in many malignancies such as breast, lung and colon cancer. They also correlate significantly with poor survival in patients as well as cancer metastasis and poor prognosis. Therefore, this paper provides a strong basis in targeted cancer therapy development.
Full article available at: http://www.jci.org/articles/view/67951
Authors : Yuan-Feng Lin, Tsung-Ching Lai, Chih-Kang Chang, Chi-Long Chen, Ming-Shyan Huang, Chih-Jen Yang, Hon-Ge Liu, Jhih-Jhong Dong, Yi-An Chou, Kuo-Hsun Teng, Shih-Hsun Chen, Wei-Ting Tian, Yi-Hua Jan, Michael Hsiao, and Po-Huang Liang
Updated : 2013.09.05 (Edited from Academia Sinica press release)