Abstract
Evidence supporting the existence of distinct transport systems for folate and methotrexate (MTX) in HeLa cells has been presented. Folate and MTX were observed not to compete with each other in competitive transport experiments in HeLa cells. The selective inhibition of folate and/or MTX transport by folate analogues further substantiated the existence of separate transport systems. 10-Oxaaminopterin inhibited the uptake of both MTX and folate, whereas 10-thioaminopterin selectively inhibited MTX uptake. The thio and oxa analogues of folic acid effectively inhibited folate transport and had a negligible effect on MTX transport. In comparison with the inhibitory activity of MTX, the oxa and thio analogues of aminopterin had a high level of antifolate activity as determined by inhibition of the incorporation of [2-14C]deoxyuridine into acid-precipitable DNA and cell growth. The potential use of 10-oxaaminopterin in the treatment of MTX-resistant forms of cancer is discussed in relation to its unique transport characteristics and its high antifolate activity.
- Copyright © 1978 by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|