Potent antitumor effects of a novel actinomycin D analog Leu5AMD.

Leu5AMD ([D-Val2, L-MeLeu5]2 AMD) is a novel actinomycin D (AMD) analog, in which both N-methylvalines were replaced by N-methylleucines. In the present study, an attempt has been made to investigate the effects of Leu5AMD on the proliferation of human gastric carcinoma cell line SGC-7901. The results showed that Leu5AMD inhibited the proliferation and induces apoptosis in SGC-7901 cells in a dose-dependent manner. Apoptosis induced by Leu5AMD was further confirmed by annexin V-FITC/PI dual staining assay. After treatment with Leu5AMD, the loss of mitochondrial potential and the decrease of bcl-2 gene expression were observed in apoptotic cells, suggesting that Leu5AMD may be involved in mitochondria and bcl-2 related apoptotic pathway. In addition, the in vivo antitumor effects of Leu5AMD on S-180 bearing mice and the acute toxicity on healthy mice were investigated. Treatment with Leu5AMD markedly suppressed the growth of Sarcoma xenograft. These results suggest that Leu5AMD may be used as a promising chemotherapeutical agent for patients affected by gastric carcinoma and other solid cancer.
AuthorsKai-Rong Wang, Bang-Zhi Zhang, Wei Zhang, Jie-Xi Yan, Xinlei Li, Rui Wang
JournalCancer letters (Cancer Lett) Vol. 268 Issue 1 Pg. 38-45 (Sep 8 2008) ISSN: 0304-3835 [Print] Ireland
PMID18448241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • actinomycin D, valyl(2,2')-N-methylleucyl(5,5')-
  • Dactinomycin
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Dactinomycin (analogs & derivatives, chemistry, pharmacology, therapeutic use, toxicity)
  • Dose-Response Relationship, Drug
  • Humans
  • Membrane Potential, Mitochondrial (drug effects)
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • Sarcoma 180 (drug therapy)
  • Stomach Neoplasms (drug therapy)
  • Xenograft Model Antitumor Assays

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