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Importance of cell cycle perturbations on the effectiveness of N ‐methylformamide and anti‐neoplastic drugs in combination
Author(s) -
Cucco C.,
D'Agnano I.,
Marangolo M.,
Candiloro A.,
Zupi G.
Publication year - 1991
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.1991.tb01158.x
Subject(s) - cytotoxic t cell , non negative matrix factorization , cell culture , cell cycle , pharmacology , cell , cancer research , chemistry , medicine , biology , in vitro , biochemistry , genetics , matrix decomposition , eigenvalues and eigenvectors , physics , quantum mechanics
Abstract. The effect of N ‐methylformamide (NMF) in combination with Adriamycin (ADM) and cis‐diamminedichloroplatinum (DDP) on the cell survival and cell cycle kinetics of two human tumour lines was assessed: HT29 colon carcinoma and M14 melanoma cells were exposed to ADM and DDP alone or in combination with a non‐cytotoxic dose of NMF, according to different schedules. The results demonstrate that NMF exposure sensitized both tumour cell lines to the lethal activity of ADM and DDP; however, reverse sequences had to be applied to reach an increase in the lethal activity of the two different drugs. The ADM‐NMF combination determined a powerful decrease in the surviving fraction of the two cell lines when ADM was given as the first agent (ADM → NMF), while the reverse sequence did not increase the ADM cytotoxic effect. With respect to the DDP‐NMF association, the sequence which accounted for a greater sensitizing effect was NMF administration followed by DDP treatment (NMF → DDP). This work demonstrates the importance of timing in combined treatments which involve NMF. A delay in cell proliferation elicited by NMF exposure could be responsible for the effectiveness of the combined treatment.

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