A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity

H. Tanino, T. Kubota, Y. Yamada, J. I. Koh, T. Takeuchi, S. Kase, Toshiharu Furukawa, M. Takahashi, S. Fukuda, N. Ogose, T. Komatsu, M. Kato, M. Kitajima, T. Sakurai, Y. Naito, R. M. Hoffman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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-1-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-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) on cells growing in monolayer culture. The 50% inhibitory concentrations (IC50) 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 IC50 of SAE9 was 5.5 x 10-7 M, which was superior to that of aminoglutethimide (AG) (3.8 x 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.

Original languageEnglish
Pages (from-to)623-626
Number of pages4
JournalAnticancer Research
Volume13
Issue number3
Publication statusPublished - 1993

Fingerprint

Altretamine
Aromatase
Aminoglutethimide
Inhibitory Concentration 50
Cell Line
Breast Neoplasms
Aromatase Inhibitors
Androstenedione
Small Cell Lung Carcinoma
Bromides
2-N,N-dimethylamino-4,6-bis(1-H-imidazol-1-yl)-1,3,5-triazine
Estrogens
Breast
Growth

Keywords

  • Aromatase-inhibitory activity
  • Hexamethylmelamine derivative
  • SAE9 antitumor activity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tanino, H., Kubota, T., Yamada, Y., Koh, J. I., Takeuchi, T., Kase, S., ... Hoffman, R. M. (1993). A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity. Anticancer Research, 13(3), 623-626.

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, Toshiharu; Takahashi, M.; Fukuda, S.; Ogose, N.; Komatsu, T.; Kato, M.; Kitajima, M.; Sakurai, T.; Naito, Y.; Hoffman, R. M.

In: Anticancer Research, Vol. 13, No. 3, 1993, p. 623-626.

Research output: Contribution to journalArticle

Tanino, H, Kubota, T, Yamada, Y, Koh, JI, Takeuchi, T, Kase, S, Furukawa, T, Takahashi, M, Fukuda, S, Ogose, N, Komatsu, T, Kato, M, Kitajima, M, Sakurai, T, Naito, Y & Hoffman, RM 1993, 'A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity', Anticancer Research, vol. 13, no. 3, pp. 623-626.
Tanino H, Kubota T, Yamada Y, Koh JI, Takeuchi T, Kase S et al. A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity. Anticancer Research. 1993;13(3):623-626.
Tanino, H. ; Kubota, T. ; Yamada, Y. ; Koh, J. I. ; Takeuchi, T. ; Kase, S. ; Furukawa, Toshiharu ; Takahashi, M. ; Fukuda, S. ; Ogose, N. ; Komatsu, T. ; Kato, M. ; Kitajima, M. ; Sakurai, T. ; Naito, Y. ; Hoffman, R. M. / A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity. In: Anticancer Research. 1993 ; Vol. 13, No. 3. pp. 623-626.
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abstract = "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-1-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-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) on cells growing in monolayer culture. The 50{\%} inhibitory concentrations (IC50) 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 IC50 of SAE9 was 5.5 x 10-7 M, which was superior to that of aminoglutethimide (AG) (3.8 x 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.",
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AU - Tanino, H.

AU - Kubota, T.

AU - Yamada, Y.

AU - Koh, J. I.

AU - Takeuchi, T.

AU - Kase, S.

AU - Furukawa, Toshiharu

AU - Takahashi, M.

AU - Fukuda, S.

AU - Ogose, N.

AU - Komatsu, T.

AU - Kato, M.

AU - Kitajima, M.

AU - Sakurai, T.

AU - Naito, Y.

AU - Hoffman, R. M.

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