| Summary: | 碩士 === 國立高雄師範大學 === 化學系 === 87 === Hepatocellular carcinoma ( HCC ) is a predominant malignancy in Taiwan. The progonosis of patients with HCC is still poor despite of improving diagnostic techniques. The poor survival was due to lack of specific anti-cancer drugs. It is imperative to develop new drugs for efficient therapy. This study aims to screen rutaceous alkaloids with anti-tumor activity for HCC. The inhibition of DNA synthesis of rutaceous alkaloids was determined by 3H-thymidine incorporation methods. The results indicated that dictamnine, r-fagarine, robustine, zanthosimuline, toddaquinoline, 2H-isoterihanine, toddaliamide
and canthin-6-one possessed a potent inhibition to human
hepatoma cell (Hep3B). The cytotoxicity of rutaceous alkaloids
was determined by lactate dehydrogenase (LDH) assay and trypan blue exclusion. The results indicated that they not possessed a potent cytotoxicity and inhibited the cell proliferation of Hep3B. The key biochemical event of apoptosis, endonucleolysis, was demonstrated by the typical“ DNA ladder ”on agarose gel electrophoresis. Then we try to analysis cell cycle, the Sub-G1 peak was negative as revealed by flow cytometer. We also investigated the downstream effectors in the apoptosis induced by zanthosimuline and 2H-isoterihanine. We found that
zanthosimuline and 2H-isoterihanine increased the expression
of Bax. Therefore, we propose that zanthosimuline and
2H-isoterihanine induces apoptosis through activation of Bax.
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