Suramin enters and accumulates in low pH intracellular compartments of v-sis-transformed NIH 3T3 cells.
Using acridine orange as a reporter compound, we demonstrate that suramin enters and accumulates in low pH intracellular compartments (endosomes, lysosomes, and trans-Golgi complex) of normal and v-sis-transformed NIH 3T3 cells. The concentration of suramin in these acidic compartments is estimated to be > 150 microM, higher than the concentration known to completely inhibit interaction of the platelet-derived growth factor (PDGF) receptor and v-sis gene product. These results support the hypothesis that suramin reverses the transformed phenotype of v-sis-transformed cells by entering the cell via endocytosis and blocking interaction of the v-sis gene product and PDGF receptor in intracellular organelles.
Huang
S S
SS
E.A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, MO 63104, USA.
Koh
H A
HA
Huang
J S
JS
D016475:3T3 Cells; D000165:Acridine Orange; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D020575:Oncogene Proteins v-sis; D015388:Organelles / Q000378:metabolism*; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis*; D013498:Suramin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology
D020575:Oncogene Proteins v-sis; D015682:Retroviridae Proteins, Oncogenic; D013498:Suramin; D017479:Receptors, Platelet-Derived Growth Factor; D000165:Acridine Orange