A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity
Tanino, H.; Kubota, T.; Yamada, Y.; Koh, J.I.; Takeuchi, T.; Kase, S.; Furukawa, T.; Takahashi, M.; Fukuda, S.; Ogose, N.
Anticancer Research 13(3): 623-626
1993
ISSN/ISBN: 0250-7005 PMID: 8317890 Document Number: 415778
Hexamethylmelamine (HMM) has previously been shown to be active against ovarian, breast and small cell lung cancer. However HMM dose not have aromatase-inhibitory activity. A newly developed HMM derivative, 2-N,N-dimethylamino-4, 6-bis (1-H-imidazol-l-yl)-1,3,5-triazine (SAE9), was found to have direct antitumor activity, as well as aromatase-inhibitory activity. The direct antitumor activity on breast carcinoma cell lines (MCF-7, R-27 and MDA-MB-231) was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) on cells growing in monolayer culture. The 50% inhibitory concentrations (IC-50) of SAE9 were found to be approximately 10-4 M for each cell line, roughly equivalent to those of HMM. When the aromatase-inhibitory effect was assessed using a human placental aromatase-inhibitory assay, the IC-50 of SAE9 was 5.5 times 10-7 M, which was superior to that of aminoglutethimide (AG) (3.8 times 10-5 M). In a rat uterine growth model treated with androstenedione as the in vivo aromatase inhibition assay, SAE9 had an effect equivalent to that of AG. Since SAE9 has both antitumor and aromatase-inhibitory activity on breast carcinoma cell lines with estrogen dependency, this and similar non-steroidal aromatase inhibitors are thought to be promising for further study.