Pre-Treatment of human osteosarcoma cells with N-methylformamide enhances P-glycoprotein expression and resistance to doxorubicin
Corresponding Author
Katia Scotlandi
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Laboratorio di Ricerca Oncologies, Istituti Ortopedici Rizzoli, Via Di Barbiano 1/10, 40136 Bologna, Italy. Fax: 39 51 584422Search for more papers by this authorMassimo Serra
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorMaria Cristina Manara
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorPier-Luigi Lollini
Istituto di Cancerologia, Universitá di Bologna, Bologna, Rome, Italy
Search for more papers by this authorDaniela Maurici
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorDonatella Del Bufalo
Laboratorio di Chemiolerapia Sperimentale, Istituto Regina Elena, Rome, Italy
Search for more papers by this authorNicola Baldini
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorCorresponding Author
Katia Scotlandi
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Laboratorio di Ricerca Oncologies, Istituti Ortopedici Rizzoli, Via Di Barbiano 1/10, 40136 Bologna, Italy. Fax: 39 51 584422Search for more papers by this authorMassimo Serra
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorMaria Cristina Manara
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorPier-Luigi Lollini
Istituto di Cancerologia, Universitá di Bologna, Bologna, Rome, Italy
Search for more papers by this authorDaniela Maurici
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorDonatella Del Bufalo
Laboratorio di Chemiolerapia Sperimentale, Istituto Regina Elena, Rome, Italy
Search for more papers by this authorNicola Baldini
Laboratorio di Ricerca Oncologica, Istituti Ortopediti Rizzoli, Bologna
Search for more papers by this authorAbstract
N-methylformamide (NMF), 3 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 osteosarcoms (OS), we have analyzed the effects of NMF and doxorubicin (DXR) or 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. © 1994 Wiley-Liss, Inc.
References
- Baldini, N., Scotlandi, K., Serra, M., Kusuzaki, K., Shikita, T., Manara, M. C., Maurici, D. and Campanacci, M., Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma. J. Cancer Res. clin. Oncol., 119, 121–126 (1992).
- Bates, S. E., Currier, S. J., Alvarez, M. and Fojo, A. T., Modulation of P-glycoprotein phosphorylation and drug transport by sodium butyrate. Biochemistry, 31, 6366–6372 (1992).
- Bates, S. E., Mickley, L. A., Chen, Y.-N., Richert, N., Rudick, J., Biedler, J. L. and Fojo, A. T., Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation. Mol. Cell. Biol., 9, 4337–4344 (1989).
-
Blaney, S. M.,
Smith, M. A. and
Grem, J. L.,
Doxorubicin: role in the treatment of osteosarcoma.
In: G. Bennett Humphrey (ed.),
Osteosarcoma in adolescents and young adults,
pp. 55–73,
Kluwer. Boston
(1993).
10.1007/978-1-4615-3518-8_10 Google Scholar
- Chin, K.-V., Tanaka, S., Darlington, G., Pastan, I. and Gottesman, M. M., Heat shock and arsenite increase expression of the multidiug resistance (MDR1) gene in human renal carcinoma cells. J. biol. Chem., 265, 221–226 (1990).
- Chomczynsky, P. and Sacchi, N., Single step method of RNA isolation by acidic guanidinium thyocyanate-phenol-chlorophorm extraction. Anal Biochem., 162, 156–159 (1987).
- Clagett-Carr, K., Sarosy, G., Plowman, J., Hoth, D. F. and Leyland-Jones, B., N-methylformamide: cytotoxic, radiosensitizer or chemosensitizer. J. clin. Oncol., 6, 906–918 (1988).
- Cucco, C., D'Agnano, L., Marangolo, M. M., Candiloro, A. and Zupi, G., Importance of cell cycle perturbations on the effectiveness of N-methylformamide and anti-neoplastic drugs in combination. Cell Prolif., 24, 293–303 (1991).
- Eton, O., Bajorin, D. F., Casper, E. S. and Houghton, A. N., Phase II trial of N-methylformamide in patients with metastatic melanoma. Invest. New Drugs, 9, 97–100 (1991).
- Fojo, A. T., Ueda, K., Slamon, D., Poplack, D., Gottesman, M. M. and Pastan, I., Expression of a multidrug-resistance gene in human tumors and tissues. Proc. nat. Acad. Sci. (Wash.), 84, 265–269 (1987).
- Greco, C., Del Bufalo, D., Giannarelli, I., Marangolo, M., Fuggetta, M. P., Bonmassar, E. and Zupi, G., N-methylformamide affects spontaneous metastases of 3II lines and increases natural killer activity of tumor-bearing mice. Clin. exp. Metastasis, 8, 153–163 (1990).
- Iwakawa, M., Tofilon, P. J., Arundel, C. and Milas, L., Combination of N-methylformamide with cis-diamminedichloroplatinum (II) in murine mammary carcinoma: importance of timing. Cancer Res., 49, 1640–1643 (1989).
- Iwakawa, M., Tofilon, P. J., Hunter, N., Stephens, L. C. and Milas, L., Antitumor and antimetastatic activity of the differentiating agent N-methylformamide in murine tumor systems. Clin. exp. Metastasis, 5, 289–294 (1987).
- Kramer, R., Weber, T. K., Arceci, R., Morse, B., Simpson, H., Steele, G. D. and Summerhayers, I. C., Modulation of mdr-1 expression by a H-ras oncogene in a human colon carcinoma cell line. Int. J. Cancer, 54, 275–281 (1993).
- Langdon, S. P., Hickman, J. A., Gescher, A., Stevens, M. F. G., Chubb, D. and Vickers, L. M., N-methylformamide (NSC 3051): a potential candidate for combination chemotherapy. Europ. J. Cancer clin. Oncol., 21, 745–752 (1985).
- Langdon, S. P., Richards, F. M. and Hickman, J. A., Investigations of the relationship between cell proliferation and differentiation of HL-60 cells induced to differentiate by N-methyl form amide. Leukemia Res., 12, 211–216 (1988).
- Laudonio, N., Zupi, G., Erba, E., Leonetti, C. and D'Incalci, M., Synergism between 5-fluorouracil and N-methylformamide in HT29 human colon cancer line. Brit. J. Cancer, 61, 377–381 (1990).
- Lotan, R., Francis, G. E., Freeman, C. S. and Waxman, S., Differentiation therapy. Cancer Res., 50, 3453–3464 (1990).
- McGuire, W. P. 3d, Blessing, J. A., Berek, J. S. and Munoz, A., Phase II study of N-methylformamide (N-MF) (NSC 3051) in patients with advanced epithelial ovarian cancer. A Gynecologic Oncology Group study. Invest. New Drugs, 8, 191–194 (1990).
- Mickley, L. A., Bates, S. E., Richert, N. D., Surrier, S., Tanaka, S., Foss, F., Rosen, N. and Fojo, A. T., Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents. J. biol Chem., 264, 18031–18040 (1989).
- Murphy, S. B., Mirro, J., Jr., Pui, C. H. and Pratt, C. B., Phase I trial of N-methylformamide in pediatric patients with refractory leukemias. Cancer Treat. Rep., 11, 1299–1300 (1987).
- Planting, A. S. T., Klign, J. G. M., Verweij, J. and Stoter, G., Phase II study on oral N-methylformamide in metastatic colorectal cancer. Cancer Treat. Rep., 71, 1293–1294 (1987).
- Schinkel, A. H. and Borst, P., Multidrug resistance mediated by P-glycoprotein. Sem. Cancer Biol., 2, 213–226 (1991).
- Scotlandi, K., Serra, M., Landuzzi, L. and Baldini, N., SARG: a new human osteosarcoma cell line. Expression of bone markers and of major histocompatibility antigens. Ann. Oncol., 3, S29–S31 (1992).
- Serra, M., Scotlandi, K., Manara, M. C., Maurici, D., Lollini, P.-L., De Giovanni, C., Toffoli, G. and Baldini, R., Establishment and characterization of multidrug-resistant human osteosarcoma cell lines. Anticancer Res., 13, 323–330 (1993).
- Stein, G. S., Lian, J. B. and Owen, T. A., Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J., 4, 3111–3123 (1990).
- Ueda, K., Clark, D. P., Chen, C., Roninson, I. B., Gottesman, M. M. and Pastan, I., The human multidrug resistance (mdr1) gene. J. boil. Chem., 262, 505–508 (1987).
- Zupi, G., Marangolo, M., Arancia, G., Greco, C., Laudonio, N., Iosi, F., Formtsano, G. and Malorni, W., Modulation of the cytotoxic effect of 5-fluorouracil by N-methylformamide on a human colon carcinoma cell line. Cancer Res., 48, 6193–6200 (1988).
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