Inhibition of Growth of Bladder Cancer Cells by 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one in Combination with Other Compounds Affecting Glucose Metabolism.
In seven out of eight human bladder cell lines that were examined herein, growth was more dependent on the presence in the incubation medium of glucose rather than glutamine. The exception was the slowly growing RT4 cells that were more glutamine-dependent. Growth of all the cell lines was reduced by an inhibitor of 6-phosphofructo-2-kinase/2,6-bisphosphatase 3, namely 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). Growth was also reduced by three compounds that reduce the conversion of glucose to lactate: namely 2-deoxyglucose, butyrate and dichloroacetate. Additive effects were seen when these molecules were combined with 3PO. Treatment of bladder cancer cells with phenformin resulted in growth inhibition that was frequently accompanied by increased glucose uptake and acidification of the medium that was blocked by co-incubation with 3PO. The actions of 3PO suggest that inhibitors of PFKB3 merit further investigation in the treatment of bladder cancer and they may be useful agents in combination with other drugs that inhibit cancer cell proliferation.
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, U.S.A. lea@njms.rutgers.edu.
Michael A
MA
Lea
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, U.S.A.
Mansour
M
Altayyar
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, U.S.A. Department of Biology, Medgar Evers College - City University of New York, Brooklyn, NY, U.S.A.
Charles
C
desBordes
D000963:Antimetabolites / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D003847:Deoxyglucose / Q000494:pharmacology*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D010629:Phenformin / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
C527590:3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one; D000963:Antimetabolites; D002087:Butyrates; D007004:Hypoglycemic Agents; D011725:Pyridines; D003847:Deoxyglucose; D003999:Dichloroacetic Acid; D010629:Phenformin; D005947:Glucose
2-deoxyglucose; Bladder cancer cells; PFKFB3 inhibitor; butyrate; dichloroacetate; glycolysis; growth; phenformin