-
Proceedings of the National Academy of... Jul 1962
Topics: Animals; Dactinomycin; Humans; Viruses
PubMed: 14491128
DOI: 10.1073/pnas.48.7.1238 -
Advances in Applied Microbiology 1973
Review
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Bacteria; Cells, Cultured; Chromatophores; Circular Dichroism; DNA; Dactinomycin; Genes; Magnetic Resonance Spectroscopy; Models, Chemical; Molecular Conformation; Neoplasms, Experimental; Optical Rotatory Dispersion; Peptides; Structure-Activity Relationship; Terminology as Topic; Virus Replication; X-Ray Diffraction
PubMed: 4131719
DOI: No ID Found -
Annals of the New York Academy of... Oct 1960
Topics: Animals; Dactinomycin; Neoplasms, Experimental
PubMed: 13723045
DOI: 10.1111/j.1749-6632.1960.tb20164.x -
The Journal of Antibiotics Feb 1969
Topics: Carbon Isotopes; Chromatography; Dactinomycin; Proline; Streptomyces
PubMed: 4181575
DOI: 10.7164/antibiotics.22.85 -
Bioorganic & Medicinal Chemistry Mar 2001An excellent anti-leukemia activity has been found in a group of actinomycin D analogues derivatized at the 2,2'- or 5,5'-position of the depsipeptides. On the basis of...
An excellent anti-leukemia activity has been found in a group of actinomycin D analogues derivatized at the 2,2'- or 5,5'-position of the depsipeptides. On the basis of the water solubilities, the DNA binding affinities, the RNA synthesis inhibitory activities, the anticancer activities of actinomycin D (AMD), and the crystal structures of DNA-AMD complexes, it becomes clear that AMD is extremely well designed as an effective poison produced by micro-organisms. The anticancer activity of AMD is mainly due to its selective inhibition of RNA synthesis. We have hypothesized that a modification on the AMD structure at a site not involved in DNA interaction can either increase or decrease the diffusion rate of the analogue into certain cancer cells. Since the i-propyl groups of the D-valine residues at the 2,2'-positions and N-methyl-L-valine residues at the 5,5'-positions in the depsipeptides do not participate in interaction with DNA, these amino acid residues were replaced with other D-amino acid residues and N-methyl-L-amino acid residues, respectively. The cancer screen tests have indicated that AMD analogues 2,2'-D-PheAMD, 2,2'-D-OmeAMD, 5,5'-L-TyrAMD, 5,5'-D-ValAMD, 5,5'-D-TyrAMD, 5,5'-D-PheAMD, and 5,5'-D-OmeAMD, inhibit selectively the growth of leukemia cell lines at about 100- to 500-fold lower drug concentrations than those required to inhibit other cancer cell lines.
Topics: Animals; Antineoplastic Agents; Binding Sites; Biological Transport; Cell Division; DNA; Dactinomycin; Humans; Inhibitory Concentration 50; Leukemia; Solubility; Structure-Activity Relationship; Transcription, Genetic; Tumor Cells, Cultured
PubMed: 11310607
DOI: 10.1016/s0968-0896(00)00293-5 -
Carcinogenesis Apr 2024There are three major subtypes of breast cancer, ER+, HER2+ and triple-negative breast cancer (TNBC), namely ER-, PR-, HER2-. TNBC is the most aggressive breast cancer...
OBJECTIVES
There are three major subtypes of breast cancer, ER+, HER2+ and triple-negative breast cancer (TNBC), namely ER-, PR-, HER2-. TNBC is the most aggressive breast cancer with poor prognosis and no target drug up to now. Actinomycin D (ActD) is a bioactive metabolite of marine bacteria that has been reported to have antitumor activity. The aim of study is to investigate whether ActD has a synergetic effect on TNBC with Doxorubicin (Dox), the major chemotherapeutic drug for TNBC, and explore the underlying mechanism.
METHODS
TNBC cell lines HCC1937, MDA-MB-436 and nude mice were used in the study. Drug synergy determination, LDH assay, MMP assay, Hoechst 33342 staining, Flow cytometry, Flexible docking and CESTA assay were carried out. The expression of proteins associated with apoptosis was checked by Western blot and siRNA experiments were performed to investigate the role of P53 and PUMA induced by drugs.
RESULTS
There was much higher apoptosis rate of cells in the ActD + Dox group than that in ActD group or Dox group. Expression of MDM2 and BCL-2 was reduced while expression of P53, PUMA and BAX were increased in the groups treated with ActD + Dox or Dox compared to the control group. Furthermore, P53 siRNA or PUMA siRNA tremendously abrogated the cell apoptosis in the groups treated by ActD, Dox and ActD + Dox. Flexible docking and CESTA showed that ActD can bind MDM2.
CONCLUSIONS
ActD had a synergetic effect on TNBC with Dox via P53-dependent apoptosis and it may be a new choice for treatment of TNBC.
Topics: Animals; Humans; Mice; Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Dactinomycin; Doxorubicin; Mice, Nude; RNA, Small Interfering; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53
PubMed: 37997385
DOI: 10.1093/carcin/bgad086 -
International Journal of Biological... Jun 2016The high mobility group box 1 protein has been identified as a key player in chromatin homeostasis including transcription regulation, recombination, repair, and...
The high mobility group box 1 protein has been identified as a key player in chromatin homeostasis including transcription regulation, recombination, repair, and chromatin remodeling. Emerging findings indicate HMGB1 protein over expression in nearly all types of human cancers and inflammatory disorders. Thus it is considered as a potential therapeutic target for treating various malignancies. We screened the promoter region of hmgb1 gene and selected a positive regulatory element of 25 base pair duplex (25RY) (-165 to -183) as a potential target for chemotherapeutic intervention. The molecular interaction of actinomycin (ACT) with the regulatory region of hmgb1 gene was characterized by spectroscopic, calorimetric and molecular docking studies. The hypochromic and bathochromic shift in the absorption spectrum, stabilization of 25RY duplex against thermal denaturation, perturbation of CD spectrum of duplex and enhancement of fluorescence intensity of actinomycin indicate strong binding of actinomycin to the hmgb1 promoter region (25RY).The energetics was characterized to be endothermic and entropy driven. All these results are in good agreement with in silico investigation that suggest minor groove binding with effective intercalation at GC bases of actinomycin to 25RY. This study identifies hmgb1 gene promoter region a potential target for the anticancer therapautiucs.
Topics: Antineoplastic Agents; Base Sequence; Dactinomycin; GC Rich Sequence; HMGB1 Protein; Molecular Docking Simulation; Nucleic Acid Conformation; Thermodynamics
PubMed: 26923673
DOI: 10.1016/j.ijbiomac.2016.02.060 -
The Medical Journal of Australia Nov 1960
Topics: Child; Dactinomycin; Humans; Infant; Neoplasms
PubMed: 13694587
DOI: 10.5694/j.1326-5377.1960.tb23781.x -
Nature Sep 1960
Topics: DNA; Dactinomycin
PubMed: 13751973
DOI: 10.1038/1871112a0 -
Nature Oct 1965
Topics: Animals; Cell Nucleus; Chick Embryo; Dactinomycin; Erythrocytes; Hemoglobins; In Vitro Techniques; Protein Biosynthesis; RNA, Messenger; Reptiles
PubMed: 5867596
DOI: 10.1038/208497b0