Dimethyladamantylmaleimide-induced in vitro and in vivo growth inhibition of human colon cancer Colo205 cells.
The effect of N-1-(3,5-dimethyladamantyl)maleimide (DMAMI) on the growth of Colo205 human colon cancer cells was examined both in vitro and in vivo. Flow cytometry analysis showed a decrease of G2/M Colo205 cells at 4-6 h after treatment with DMAMI prior to accumulation of apoptotic cells at 24 h. Significant changes in cell morphology, i.e. shrinkage and chromatin condensation of cells, were observed after treatment with DMAMI. In the analysis of the apoptosis markers, it was found that the increase of Annexin V binding to membrane, peroxide radicals, dissipation of the mitochondrial membrane potential, and the activation of caspase-3, -8 and -9 were all evident at 4-6 h after treatment with DMAMI. In vivo analysis showed that treatment of Colo205 tumor-bearing SCID mice with DMAMI (230 mg/kg, intratumoral, once) resulted in rapid tumor damage that leads to significant tumor growth inhibition and no obvious acute toxicity. These results suggest that DMAMI has potential for local treatment of cancer.
Wang
Jane-Jen
JJ
National Taipei College of Nursing, Taipei, Taiwan 11219, ROC.
Chern
Yaw-Terng
YT
Chang
Yuh-Fang
YF
Liu
Tsung-Yun
TY
Chi
Chin-Wen
CW
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008301:Maleimides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009336:Necrosis; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D017304:Annexin A5; D000970:Antineoplastic Agents; D003574:Cytochrome c Group; D005609:Free Radicals; D008301:Maleimides; C469820:N-1-(3,5-dimethyladamantyl)maleimide; D020169:Caspases; D000218:Adamantane