Characterization the anti-cancer effects of BMVC derivatives

• Main Authors: Chih-Yu Feng, 馮芝渝
• Other Authors: Jing-Jer Lin
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/40200644162172374665

碩士 === 國立陽明大學 === 生物藥學研究所 === 101 === G-quadruplexes are special DNA secondary structures formed by non-Watson-Crick base-pairing of guanines. G-quadruplexes are widely distributed in chromosomes such as telomeres or promoters of some oncogenes. Because telomerase cannot utilize G-quadruplex structure as substrate to extend telomeres and formation of G-qrudplex structures at the promoter regions suppress the expression of several oncogenes, G-quadruplexes stabilizer has potential to be developed into anti-cancer agent. Previously we have identified small compound BMVC that stables G-quadruplex structures and inhibits tumorigenesis. Here we further characterize the anti-cancer properties of several BMVC derivatives. Two series of BMVC derivatives were synthesized through the collaboration with Dr. Chang, Ta-Chau (Academia Sinica) and Dr. Chen, Chao-Tsen (National Taiwan University). The telomerase inhibitory activities of these compounds were analyzed by TRAP assays and the anti-proliferation and senescence-induction activities of these compounds toward cancer cells were analyzed using resazurin test and senescence associated--Gal assay, respectively. We found several of the tested BMVC derivatives effectively inhibit telomerase activity. They effectively induced cancer cells into senescence. Moreover, we identified one compound that showed selective cytotoxic toward cancer cells. It is known that BLM is a helicase that catalyzes the resolving activity of G-quadruplex structures. The role of BLM in BMVC derivatives-induced senescence was also analyzed. We found knocking down BLM did not appear to affect the DNA damage response induced by BMVC derivatives. Together, the results indicate that BMVC and its derivatives have potential to be further developed into anti-cancer drugs. BLM might not be involved in resolving BMVC derivative-stabilized G quadruplex structures.