Chemoprevention and anticancer effects of an urushiol from Rhus succedanea

• Main Authors: Nai-Hui Chi, 紀乃卉
• Other Authors: 林淑萍
• Format: Others
• Language: en_US
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/12534823796284066855

碩士 === 國立臺灣大學 === 醫事技術學研究所 === 93 === A novel urushiol, 10’(Z),13’(E),15,(E) -Heptadecatrienylhydroquinone (HQ173) purified from sap of the lacquer trees, Rhus succedanea, was found to inhibit several tumor cell lines growth and induced cell apoptosis. In the present study, we found HQ173 at low dosage (less than 1 uM) did not have cytotoxity in PBMC, and could overcome the oxidative toxicity of DL-Buthionine- [S,R]-sulfoximine (BSO). Results of this study in PBMC indicated that cellular sulfhydryl (SH) was depleted 13% at 30 min after HQ173-treatment and returned to original level after 2 hr. HQ173 could induce Nrf2 nuclear translocation at 2 hr after treatment. More nuclear Nrf2 were detected after 4 hr. NQO1 mRNA level and GST enzyme activity were induced by HQ173. Three major mitogen-activated protein kinases (MAPK) were activated after HQ173-treatment. We supposed that the p38 phosphorylation was induced by HQ173, which caused Nrf2 translocation to influence the downstream genes expression. On the other hand, those phenomenons were not found in HL-60 cells. The in vivo experiment was also observed. We found HQ173 could inhibit tumor growth in F-344 rats, and did not affect the growth of rats. The data of clinical chemistry showed there were no hepatoxicity and renal toxicity by intraperitoneal (ip) administration of HQ173. We hypothesized that HQ173 could induce immune response to cause tumor cell apoptosis, and proceed to the next step to cause inhibition of tumor growth in vivo. This study would verify that HQ173 had dual effects. First, HQ173 at low dosage could induce chemoprevention to protect cells against oxidants in PBMC. We considered the chemoprevention effect of HQ173 could protect normal cells, but not tumor cells. Second, HQ173 could inhibit hepatoma growth in vivo. To sum up, HQ173 would be worth to develop for chemoprevention and cancer therapy.