Inhibition of murine leukemia (WEHI-3B and L1210) proliferation by cholera toxin B subunit.
Cholera holotoxin produces both stimulation and inhibition of the growth of different cell populations. These opposite effects were both attributed to the enzymatic activity of the subunit A that activates adenylate cyclase, increasing the intracellular level of cAMP. We observed that the B subunit of cholera toxin produced by itself an inhibition of the 'in vitro' growth of two murine leukemia cell lines (L1210 limphoid leukemia and WEHI-3B myelomonocytic leukemia). The sensitivity of WEHI-3B cells towards cholera toxin was about 5000-times higher than that of the L1210 cells, whereas the two leukemias showed an identical sensitivity to the B subunit (IC50 = 5.10(-10) M for L1210 and 10(-10) M for WEHI-3B). The inhibition produced by the B subunit was neutralized by GM1 and in a minor degree by type II gangliosides. The two leukemias showed a remarkable difference in their gangliosides contents (L1210 cells contained GM1 (80.6%) and GM2 (19.4%), while WEHI-3B cells contained GM1 (28.2%), Fuc-GM1 (44.9%) and a band (26.9%) with a chromatographic mobility between GD1a and GD1b). The inhibition could be explained by a competitive mechanism between the B subunit and some autocrine factor binding GM1-containing receptors. Our data strengthen the suggestion to consider gangliosides as very important pleiotropic biomodulators.
Pessina
A
A
Institute of Medical Microbiology, University of Milan, Italy.
Mineo
E
E
Masserini
M
M
Neri
M G
MG
Cocuzza
C E
CE
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005260:Female; D005677:G(M1) Ganglioside / Q000032:analysis / Q000494:pharmacology; D005732:Gangliosides / Q000032:analysis / Q000494:pharmacology; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology*; D007942:Leukemia, Experimental / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D005732:Gangliosides; D010446:Peptide Fragments; D005677:G(M1) Ganglioside; C050310:cholera toxin, B subunit (50-64); D002772:Cholera Toxin