Selective antiproliferative effects of thymidine.

A substance with antiproliferative bioactivity in an aqueous extract of Cordyline terminalis was purified and identified by mass spectrometry to be the natural nucleoside, thymidine. 10(-5) M Thymidine inhibited EL4 cell replication and decreased cell viability after 12-24 h. The effect was highly specific for this nucleoside. Treated cell cultures showed a significant increase in S phase cells and a corresponding decrease in G1 phase cells. Nitrobenzylthioinosine (which prevented facilitated entry of thymidine) protected cells from the antiproliferative action of thymidine. A human breast cancer cell line (MCF7) was also growth-inhibited by 10(-5) M thymidine but a murine lymphoma cell line (K36) was not. Thus, submillimolar thymidine has effects on cell proliferation which are selective both with respect to specificity for the compound and for different tumour cell lines.