Investigation of the Cellular Cytotoxicity and Action Mechanism Induced by BMVC and Related Photosensitizers

• Main Authors: Shang-Chih Chen, 陳尚志
• Other Authors: Chin-Tin Chen
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/52604274487037083664

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 94 === Presently, the major obstacle of cancer chemotherapy is the non-specific cytotoxicity of chemotherapeutic drugs. Over 80% of cancer cells maintain telomere length by telomerase, which are not found in normal somatic cells. Therefore telomerase inhibitor could induce selective cytotoxicity on tumor cell. 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) has been synthesized and shown to stabilize the G-quadruplex structure of human telomeric sequence of d(T2AG3). The purpose of this study is to investigate the biological effects of BMVC on HeLa cell. We found: (1) The growth of tumor cells was inhibited by BMVC. (2) The long-term effects in population doubling showed that the growth inhibition of BMVC and the shortening of telomere by BMVC might not play the major role in the inhibition of cell growth. (3) Compared to normal cells, cancer cells have higher uptake of BMVC. (4) BMVC was mainly localized in the nucleus of cancer cells (5) BMVC suppressed the cell progression cycle into S-phase. (6) BMVC could interfere to form relax induced by Topoisomerase II. Furthermore, we investigated the cellular location, uptake, and photodynamic effects of BMVC analogs and Meto-tera (hydroxyphenyl) porphyrin derived analogs.