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 17beta-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 x 10(-8) M. Both fenvalerate (1 x 10(-6) M) and permethrin (1 x 10(-6) M) did not stimulate the AlkP activity, but progesterone (1 x 10(-8) M)-induced AlkP activity was significantly inhibited at 1 x 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 x 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.

• Authors: In Young Kim, Soon Young Han, Tae Seok Kang, Byung Mu Lee, Kwang Sik Choi, Hyun Ju Moon, Tae Sung Kim, Il Hyun Kang, Seung Jun Kwack, Aree Moon, Mee Young Ahn, Hyung Sik Kim
• Journal: Journal of toxicology and environmental health. Part A (J Toxicol Environ Health A) Vol. 68 Issue 23-24 Pg. 2175-86 (Dec 10 2005) ISSN: 1528-7394 [Print] England
• PMID: 16326432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insecticides
• Nitriles
• Pyrethrins
• Receptors, Progesterone
• Progesterone
• Permethrin
• Alkaline Phosphatase
• fenvalerate

Topics

• Alkaline Phosphatase (antagonists & inhibitors, metabolism)
• Breast Neoplasms
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Insecticides (toxicity)
• Nitriles (toxicity)
• Permethrin (toxicity)
• Progesterone
• Pyrethrins (toxicity)
• Receptors, Progesterone (metabolism)