chromomycin-a3 and Stomach-Neoplasms

A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins A2 (1) and A3 (2). 1 and 2 showed potent cytotoxicity against the human gastric adenocarcinoma (AGS) cell line (IC50 1; 1.7 and 2; 22.1 nM), as well as strong inhibitory effects against TCF/β-catenin transcription (IC50 1; 1.8 and 2; 15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the effects of chromomycins A2 (1) and A3 (2) on TRAIL resistance-overcoming activity, and on the Wnt signaling pathway, have not been reported previously. Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant and Wnt signal-related diseases and offer potentially useful chemical probes for investigating TRAIL resistance and the Wnt signaling pathway.

Topics: Actinobacteria; Adenocarcinoma; Antineoplastic Agents; Cell Line, Tumor; Chromomycin A3; Geologic Sediments; Humans; Inhibitory Concentration 50; Plicamycin; Stomach Neoplasms; TNF-Related Apoptosis-Inducing Ligand; Wnt Signaling Pathway

For the remission induction therapy of advanced gastric and rectal cancer, 25 cases were treated by non-radical irradiation (total doses: 3000-6000 rad) combined with tegafur, which minimized the tumor mass. For the reduction of tumor mass, a modified method of FAMT was employed and for the maintenance therapy of long-term chemotherapy a modified method of FAMT, MFE, MF or tegarfur alone were performed. Prolongation in survival was obtained with this combination therapy: Of 25 cases, 11 cases survived longer than one year and 6 cases longer then two years. One case of survived rectal cancer obtained disease-free for about 8 years with this treatment. But the observation period was too short to calculate one-year and two-year survival rates of all cases. The indications for application of this combination therapy were as follows; (1) Locally operable cases with myocardial infarct, heart insufficiency, poor risk or refusal of operation, (2) Very aged patients, (3) Locally inoperable cases without clinical metastasis, and (4) Primary lesion of gastric cancer with small metastasis controllable by tegafur. It was concluded that over 3000 rad of irradiation combined with tegafur was necessary to obtain the sufficient radiation effect. As for side effects, loss of appetite , leukopenia and a few case of gastric bleeding by radiation were noted. From the result this treatment modality appears to be valuable in the management of gastric and rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromomycin A3; Combined Modality Therapy; Cyclophosphamide; Humans; Radiotherapy Dosage; Rectal Neoplasms; Stomach Neoplasms; Tegafur

Topics: Adult; Aged; Anemia, Hemolytic; Antineoplastic Agents; Aspirin; Chromomycin A3; Dipyridamole; Female; Fluorouracil; Humans; Male; Mitomycin; Mitomycins; Stomach Neoplasms