Anticancer activity and mechanisms of norcantharidin-Nd3II on hepatoma.
Norcantharidin (NCTD), a demethylated form of cantharidin, is currently used as an anticancer drug in China, but five newly synthesized derivatives have not been tested for antitumor efficacy. In this study, we investigated the in-vitro and in-vivo activity of five derivatives on Bel-7402, HeLa and PC-3M1E8 cell lines on a sulfarhodamine B assay. All of the derivatives showed significant antiproliferative activity, hence we elected to study further one of them, NCTD-Nd3II, in an in-vivo mouse model, and to examine its effects on cell cycle and protein expression. NCTD-Nd3II inhibited H22 tumors in mice in a dose-dependent manner with low toxicity. Flow cytometry results showed that apoptosis and G2/M cell cycle arrest contributed to the cytotoxic and cytostatic effects of NCTD-Nd3II. Further studies showed that Bax and p21 protein expression was upregulated, whereas cyclin B1, Cdc-2 and Bcl-2 protein expression was downregulated. Our findings show that NCTD-Nd3II might be a promising chemotherapeutic agent for hepatomas.
Yang
Huayu
H
State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, PRC.
Guo
Wei
W
Xu
Bo
B
Li
Min
M
Cui
Jingrong
J
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009354:Neodymium; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D009354:Neodymium; C069741:norcantharidin; D016203:CDC2 Protein Kinase