Pyrethroid Insecticides, Fenvalerate and Permethrin, Inhibit Progesterone-Induced Alkaline Phosphatase Activity in T47D Human Breast Cancer Cells

Abstract

Pyrethroid insecticides exhibited a weak estrogenic activity by stimulation of MCF-7 cell proliferation and induction of alkaline phosphatase (AlkP) enzyme activity in cultured Ishikawa cells. Previously it was reported that fenvalerate and permethrin significantly inhibited the 17β-estradiol-induced MCF-7 BUS cell proliferation. Although certain pyrethroid insecticides exert estrogenic or antiestrogenic activities, it is not clear whether pyrethroid insecticides act as progesterone agonists or antagonists. Therefore, the aim of this study was to evaluate the effects of fenvalerate and permethrin on AlkP activity as a progesterone-specific response in T47D cells. In the present study, the stimulation of AlkP activity was concentration dependent with addition of progesterone, and maximum activity was observed at concentration of 1 × 10⁻⁸ M. Both fenvalerate (1 × 10⁻⁶ M) and permethrin (1 × 10⁻⁶ M) did not stimulate the AlkP activity, but progesterone (1 × 10⁻⁸ M)-induced AlkP activity was significantly inhibited at 1 × 10⁻⁶ M concentration of fenvalerate and permethrin, respectively. Progesterone receptor (PR) levels in cytosolic protein of T47D cells were studied to determine the relationship between cellular PR expression and AlkP activity. Similar to AlkP activity, progesterone (1 × 10⁻⁸ M) significantly increased PR protein levels compared to control. However, PR protein levels were not affected in T47D cells cultured with fenvalerate and permethrin alone, whereas fenvalerate and permethrin significantly decreased progesterone-induced PR protein levels. Our data indicate that fenvalerate and permethrin exhibit antiprogestagenic activity in T47D human breast cancer cells.

This study was supported by the Endocrine Disruptor Research Grant (ED2003) from the National Institute of Toxicological Research (NITR)/Korea Food & Drug Administration (KFDA) and supported in part by grants from the College of Pharmacy, Pusan National University.