Circumventing multidrug resistance in cancer by beta-galactoside binding protein, an antiproliferative cytokine.
We report here that beta-galactoside binding protein (betaGBP), an antiproliferative cytokine which can program cancer cells to undergo apoptosis, exhibits equal therapeutic efficacy against cancer cells that display diverse mechanisms of drug resistance and against their parental cells. The mechanisms of drug resistance in the cancer cells that we have examined include overexpression of P-glycoprotein, increased efficiency of DNA repair, and altered expression and mutation in the topoisomerase I and II enzymes. We also report that betaGBP exerted its effect by arresting the cells in S phase prior to the activation of programmed cell death. The uniquely similar profile of response to betaGBP by these drug-resistant cells and their parental cells extends the therapeutic potential of this cytokine in the treatment of cancers and offers a promising alternative to patients whose tumors are refractory to the currently available cadre of chemotherapeutic agents.
Ravatn
Roald
R
Department of Chemical Biology, Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, USA.
Wells
Valerie
V
Nelson
Leigh
L
Vettori
David
D
Mallucci
Livio
L
Chin
Khew-Voon
KV
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017209:Apoptosis; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D037161:Galectins / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D016196:S Phase; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D037161:Galectins; D011994:Recombinant Proteins; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II