A novel phenoxazine derivative suppresses proliferation of human endometrial adenocarcinoma cell lines, inducing G2M accumulation and apoptosis

Nakada,Toshihide; Isaka,Keiichi; Nishi,Hirotaka; Osakabe,Yumi; Shimamoto,Takashi; Ohyashiki,Kazuma; Tomoda,Akio; Takayama,Masaomi

doi:10.3892/or.10.5.1171

September-October 2003 Volume 10 Issue 5

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September-October 2003 Volume 10 Issue 5

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Article

A novel phenoxazine derivative suppresses proliferation of human endometrial adenocarcinoma cell lines, inducing G2M accumulation and apoptosis

Authors:
- Toshihide Nakada
- Keiichi Isaka
- Hirotaka Nishi
- Yumi Osakabe
- Takashi Shimamoto
- Kazuma Ohyashiki
- Akio Tomoda
- Masaomi Takayama
View Affiliations / Copyright

Affiliations: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan
Pages: 1171-1176
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Published online on: September 1, 2003

https://doi.org/10.3892/or.10.5.1171
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Abstract

We examined the effects of a novel phenoxazine, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx), which was produced by the reaction of 2-amino-5-methyl-phenol with bovine hemoglobin on the proliferation of human endometrial adenocarcinoma cell lines, EN and KLE cells, and on induction of apoptosis and G2M arrest in these cells. Phx inhibited proliferation of these cell lines in a dose- and time-dependent manner, i.e., the inhibition rate of proliferation of EN and KLE cells was 43% and 40%, respectively, in the presence of 50 µM Phx, and 75% and nearly 100%, in the presence of 100 µM Phx, after 2 days. When these endometrial adenocarcinoma cells were incubated with a medium containing 100 µM Phx for 24 h, accumulation of EN and KLE cells in the S and G2M phase and that of apoptotic cells were demonstrated by flow cytometry. Apoptosis of these cells caused by Phx was unlikely to be associated with p53, Bax, and Bcl-2, because the levels of these proteins were not altered regardless of the presence or absence of Phx. The present results suggest that Phx demonstrates antitumor activity against human endometrial adenocarcinoma cell lines EN and KLE cells, by inducing both cell cycle accumulation at S and G2M and apoptosis associated with p53, Bcl-2 and Bax insensitive pathways.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A novel phenoxazine derivative suppresses proliferation of human endometrial adenocarcinoma cell lines, inducing G2M accumulation and apoptosis

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Abstract

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