Pre-treatment of human osteosarcoma cells with N-methylformamide enhances P-glycoprotein expression and resistance to doxorubicin.
N-methylformamide (NMF), a powerful differentiating agent, has been extensively used in experimental and preclinical cancer chemotherapy studies, alone or in association with conventional anti-cancer drugs. To evaluate the use of this molecule in the treatment of osteosarcoma (OS), we have analyzed the effects of NMF and doxorubicin (DXR) on DXR-sensitive and -resistant human OS cell lines. Our study shows that NMF exerts remarkable effects on cell proliferation and, in Saos-2 and SARG cells, also induces differentiation, as shown by increasing alkaline phosphatase activity. Moreover, NMF increases the cytotoxic activity of DXR when administered after the drug, in both DXR-sensitive and -resistant cells. However, when this agent is given before DXR, it enhances P-glycoprotein expression in U-2 OS cell lines. This over-expression is associated with reduced DXR accumulation within cells and with significant enhancement of resistance to DXR.
Scotlandi
K
K
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Serra
M
M
Manara
M C
MC
Lollini
P L
PL
Maurici
D
D
Del Bufalo
D
D
Baldini
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005559:Formamides / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D005559:Formamides; D008562:Membrane Glycoproteins; D004317:Doxorubicin; D014700:Verapamil; C002950:methylformamide