UBC Theses and Dissertations
Anticancer activity of 20(s) protopanaxadiol on cancer cells Zhao, Yan
Current anticancer therapy is often ineffective resulting in tumor relapse due to factors including multiple drug resistance and minimal residual diseases. In this study, 20(S)-protopanaxadiol (aPPD), one of the aglycone metabolic products of ginsenosides in human gastrointestinal tract, has been characterized and shows strong anticancer anticancer activities. It can induces apoptosis in glioma and other cancer cells through multiple apoptotic pathways, and synergistically enhances the efficacy of chemotherapeutic drugs in multi-drug resistant cancer cells. The ability of aPPD to reverse p-glycoprotein (p-gp) mediated multidrug resistance was determind, aPPDresistant glioma cell lines were established and the difference of the gene expression profiles of both aPPD resistant and sensitive cell lines was exhibited. The results showed that aPPD inhibits the activity of P-gp in multiple drug resistant cell lines MCF-7adr and P388adr through a mechanism that is different from that of verapamil, a typical P-gp blocker. The aPPD-resistant glioma SF188C2R2 cells displayed crossresistance to several chemotherapeutics and lost the ability of G2-arrest caused by aPPD in the parental cells. Gene expression profiles of resting SF188 and SF188C2R2 are very different than in cells treated with aPPD. Fifty-eight percent of genes were differentially expressed in these two cell lines at resting status. In the presence of aPPD, SF188 had 10-fold more genes changed in their expression than in SF188C2R2. These results demonstrated that this compound has the potential to be developed as an anti-cancer drug for clinical application. Further analysis of validated gene expression profdes of the SF188 and its aPPD-resistant cell line SF188C2R2 may reveal the mechanisms of anticancer effects by aPPD.
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