Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tumor cell membranes were susceptible to the action of Clostridium perfringens
phospholipase C
, and this was reflected by inhibition of cellular replication in culture. The differential susceptibility of two neoplastic cell lines to this enzyme was studied in detail. The growth of
sarcoma 180
cells cultured in Fischer's medium was markedly inhibited by
phospholipase C
; whereas, in contrast, cultured L1210 leukemia cells were relatively resistant to the cytotoxic effects of this enzyme. The differential sensitivity of these two neoplastic cell lines to
phospholipase C
was corroborated by dye-exclusion tests. Thus, leukemia L1210 cells exposed to a concentration of 0.2 mg of
phospholipase C
per ml of Fischer's medium for 30 min at 37 degrees C were able to exclude Trypan Blue; whereas, only about 21% of
sarcoma 180
cells treated under identical conditions were able to exclude the dye. That the cytotoxicity of
phospholipase C
to
sarcoma 180
was the result of hydrolysis of phospholipids of the plasma membrane was supported by measurements of the rate of hydrolysis of radioactivity from the phospholipid of neoplastic cells prelabeled with [3H]choline. Eighty-two percent of incorporated radioactive choline was released from
sarcoma 180
cells treated with
phospholipase C
in Fischer's medium, whereas, only 20% of the label from [3H]choline was solubilized from L1210 leukemia cells treated with the enzyme under similar conditions. Scanning electron microscopy revealed significant damage to
sarcoma 180
cells exposed to
phospholipase C
in Fischer's medium, which was characterized by alterations in size and shape of cells, disappearance of microvilli, and appearance of fistulas in cell membranes; relatively resistant L1210 leukemic cells did not appear to be markedly damaged by comparable enzyme treatment. Exposure of leukemia L1210 cells to
phospholipase C
in Puck's saline A increased the sensitivity of these cells to enzymatic action. Under these conditions, a comparable amount of phospholipid was hydrolyzed from surface membranes of
sarcoma 180
and leukemia L1210 cells, and the degree of membrane damage appeared to be similar, as measured by the capacity of the tumor cell lines to exclude Trypan Blue and by scanning electron microscopy. The extensive damage to membranes by hydrolysis of phospholipids was not accompanied by a change in the degree of specific binding of [3H]concanavalin A(ConA).(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Combination chemotherapy with Clostridium perfringens phospholipase C and cytosine antimetabolites: complementary inhibition directed at membrane lipids. 608 55
