Studies on the induction of cell cycle arrest and apoptosis in human prostate carcinoma cells by dibenzoylmethane and its derivatives

• Main Authors: Ming-Hui Chen, 陳明慧
• Other Authors: Tzou-Chi Huang
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/44604896906737021313

碩士 === 國立屏東科技大學 === 食品科學系所 === 95 === Prostate cancer (CaP) ranks as the most common noncutaneous malignancy and the second leading cause of cancer-related deaths in American males. The incidence and mortality of prostate cancer has been rapidly increasing in the past decade in Taiwan. The major cause of mortality from this disease is metastasis of hormone refractory cancer cells that fail to respond to hormone ablation therapy. Because surgery and current treatment options have proven to be inadequate in treating and controlling CaP, the search for novel targets and mechanism-based agents for prevention and treatment of this disease has become a priority. DBM (dibenzoylmethane) and its derivatives [HDB (1-(2-Hydroxyphenyl)-3-phenyl-1, 3-propanedione) , HMDB (1-(2-Hydeoxy-5-methylphenyl)-3-phenyl-1, 3-propanedione)] from Glycyrrhiza glabra L. have been known to induce cytostatic or oncolytic effects in a variety of cancers, but few studies about DBM and its derivatives on prostate cancer cells have been performed. This study was to evaluate the induction of cell cycle arrest and apoptosis in human prostate carcinoma cells by DBM and its derivatives. Our studies demonstrated that DBM and its derivatives treatment of PC-3 cells resulted inhibited cells proliferation following and cell cycle arrest. The comparison of PC-3 cells proliferation following with DBM and its derivatives, HMDB has the best inhibit efficiently, HDB and DBM. To evaluate the effect of DBM and its derivatives on cell cycle arrest in PC-3 cells. Results showed that DBM markedly inhibited cell cycle arrest, following HDB and HMDB. To explore the molecular mechanism, we found that DBM and its derivatives treated PC-3 cells reduced the expression of cyclin D1, D3 and CDK-4, especially in cyclin D1 and cyclin D3; but no effect on CDK-2 and cyclin E. Cyclin dependent kinase inhibitors (CKI/CDKI) p27, p21 were increase after DBM, HDB and HMDB treatment, protein expression of P-Rb was decrease. We observe the of phosphorylation MAPK signaling cascades JNK, P-JNK and the protein expression of ERK-1/2 and P- ERK-1/2 were increased, but do not effect expression of p38 and P-p38 proteins after 100 µM DBM treatment during time period. The PC-3 cell treatment of PC-3 cells with different concentrations of HMDB, we found that nuclear condensation and apoptotic bodies using optical microscope. We next quantified the extent of apoptosis induced by HMDB using flow cytometric analysis. HMDB treatment the results showed that Sub G1 peak marked increase in a dose-dependent manner. Further more we observe HMDB caused DNA fragmentation in a time-dependent manner. Take together, the structure-activity relationship (SAR), We suggest that DBM inhibited cells proliferation of prostate cancer PC-3 cells is mediated through inducing cell cycle arrest, however, HMDB is through inducing cell apoptosis.