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Oncology reports

Suppression of the proliferation of cancer cell lines, KB-3-1 and K562 cells preceded by a decrease in intracellular pH caused by phenoxazine derivatives.


PMID 18425384

Abstract

The intracellular pH (pHi) of cancer cells such as the KB-3-1 (human epidermoid carcinoma cell line) and K562 cells (human chronic myeloid leukemia cell line) cultured in a medium (pH 7.4) was found to be much higher (pH 7.65 and 7.8, respectively) than that of normal cells (pHi is usually < or =7.2). When a phenoxazine derivative, 2-aminophenoxazine-3-one (Phx-3) or 2-amino-4,4alpha-dihydro-4alpha-7-dimethyl-3H-phenoxazine-3-one (Phx-1) was added to these cells, pHi rapidly decreased within 20 min, dose-dependently, though the extent of the decrease of pHi was significantly larger for Phx-3 (a decrease of 0.9 units) than for Phx-1 (a decrease of 0.4 units). Phx-3 and Phx-1 caused the proliferative suppression of these cells 24 h after the addition, dose-dependently. The anti-proliferative effects of Phx-3 on KB-3-1 and K562 cells were far greater than those of Phx-1. It was proposed that the proliferative suppression of KB-3-1 and K562 cells caused by Phx-3 and Phx-1, may be preceded by a rapid and extensive decrease in pHi, which possibly influenced the intracellular homeostasis, finally causing the suppressed proliferation and apoptosis of these cancer cells. The present results suggest that the anti-cancer effects of Phx-3 and Phx-1 may be strengthened by the intracellular acidification of cancer cells by these compounds.

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