Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of saframycin was examined against four different experimental tumor systems in mice. Saframycin A and C inhibited the growth of L1210 cells in suspension culture completely at concentrations of 0.02 microgram/ml and 1.0 microgram/ml, respectively. The LD50's of saframycin A for ddY mice were 4.9 mg/kg (ip) and 3.3 mg/kg (iv), respectively. In C3H/He mice, the LD50's were 10.5 mg/kg (ip) and 9.7 mg/kg (iv), respectively. Saframycin A was highly active against Ehrlich ascites carcinoma and P388 leukemia, and moderately active against L1210 leukemia and B16 melanoma. The antitumor activity of saframycin A was 50 to 100 times greater than that of saframycin C. The survivors cured of Ehrlich ascites carcinoma by treatment with saframycin A developed a resistance to rechallenge with the same tumor. On the other hand, when carbazilquinone and adriamycin were used as reference drugs, the cured mice in these cases did not resist rechallenge with the same tumor. When saframycin A (5 mg/kg) was administered intraperitoneally into mice, the blood concentration of saframycin A was 4.6 microgram/ml after 30 min, and 2.8 microgram/ml after 1 hr, and the total recovery within 3 hr from the urine was 30%. Saframycin A was found to be distributed widely, though to different extents, in various organs when injected intraperitoneally into mice.
 ...
PMID:Some chemotherapeutic properties of two new antitumor antibiotics, saframycins A and C. 727 25

Saframycin A (SafA) is a member of a class of natural products with potent antiproliferative effects in leukemia- and tumor-derived cells. This activity is frequently conjectured to derive from the ability of saframycins to covalently modify duplex DNA. We used a DNA-linked affinity purification technique to identify GAPDH as a protein target of DNA-small molecule adducts of several members of the saframycin class. Nuclear translocation of GAPDH occurs upon treatment of cancer cells with saframycins, and depletion of cellular GAPDH levels by small interfering RNA transfection confers drug resistance. Roeder and coworkers have recently suggested that GAPDH is a key transcriptional coactivator necessary for entry into S phase. Our data suggest that GAPDH is also capable of forming a ternary complex with saframycin-related compounds and DNA that induces a toxic response in cells. These studies implicate a previously unknown molecular mechanism of antiproliferative activity and, given that one member of the saframycin class has shown efficacy in cancer treatment, suggest that GAPDH may be a potential target for chemotherapeutic intervention.
 ...
PMID:Identification of GAPDH as a protein target of the saframycin antiproliferative agents. 1507 82