decursin and Urinary-Bladder-Neoplasms

Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, has demonstrated anti-cancer properties. In the present study, we found that decursin inhibited cell viability in cultured human urinary bladder cancer 235J cells and colon cancer HCT116 cells. The inhibited proliferation was due to apoptotic induction, because both cells treated with decursin dose-dependently showed a sub-G1 phase accumulation and an increased cytoplasmic DNA-histone complex. Cell death caused by decursin was also associated with the down-regulation of anti-apoptotic factor Bcl-2 and the up-regulation of pro-apoptotic molecules cytochrome c, caspase 3 and Bax. Treatment of both types of cancer cells with decursin resulted in G1-phase cell cycle arrest, as revealed by FACS analyses. In addition, decursin increased protein levels of p21WAF1 with a decrease in cyclins and cyclin dependent kinases (CDKs). Furthermore, decursin induced the activation of extracellular signal-regulated kinases (ERK) in both cancer cell lines, with the notable exceptions of c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase. Finally, pretreatment with ERK-specific inhibitor PD98059 reversed decursin-induced p21WAF1 expression and decursin-inhibited cell growth. Thus, these findings suggest that decursin has potential therapeutic efficacy for the treatment of bladder and colon cancer.

Topics: Apoptosis; bcl-2-Associated X Protein; Benzopyrans; Butyrates; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cytochromes c; Down-Regulation; Drug Screening Assays, Antitumor; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; G1 Phase; Humans; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Protein Kinase Inhibitors; Up-Regulation; Urinary Bladder Neoplasms

To screen antitumor active compounds, drug-like or leading compounds from Chinese traditional and herbal drugs.. Eleven coumarin compounds isolated from the Chinese traditional and herbal drugs were studied for their antitumor activities in vitro by determining the inhibition rates against growth of human bladder carcinoma cell line E-J.. It showed that umbelliferone, scoparone, demethylfuropinarine, isopimpinellin, forbesoside, columbianadin, decursin and glycycoumarin inhibited the growth of human bladder carcinoma cell line E-J in vitro and their activities showed a concentration-effect relationship. The inhibitory effects of forbesoside, columbianadin, decursin and umbelliferone, with IC50 values of 7.50x10(-7), 2.30x10(-6), 6.00x10(-6) and 1.30x10(-6) mol/L, respectively, were stronger than those of the other tested compounds. However, xanthotoxin, esculin and sphondin did not inhibit the growth of human bladder carcinoma cell line E-J in this assay condition.. These findings indicate that forbesoside, columbianadin, esculin, decursin and umbelliferone would be effective or regarded as potent drug-like or leading compounds against human bladder carcinoma.

Topics: Antineoplastic Agents, Phytogenic; Benzopyrans; Butyrates; Cell Line, Tumor; Cell Proliferation; Coumarins; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esculin; Humans; Molecular Structure; Umbelliferones; Urinary Bladder Neoplasms