Importance of cell cycle perturbations on the effectiveness of N-methylformamide and anti-neoplastic drugs in combination.
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.
Cucco
C
C
Laboratory of Experimental Chemotherapy, Regina Elena Institute for Cancer Research, Rome, Italy.
D'Agnano
I
I
Marangolo
M
M
Candiloro
A
A
Zupi
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms; D004317:Doxorubicin / Q000494:pharmacology; D005434:Flow Cytometry; D005559:Formamides / Q000494:pharmacology; D006801:Humans; D008546:Melanoma, Experimental; D014407:Tumor Cells, Cultured
D005559:Formamides; D004317:Doxorubicin; D002945:Cisplatin; C002950:methylformamide