Pyrethroid insecticides, fenvalerate and permethrin, inhibit progesterone-induced alkaline phosphatase activity in T47D human breast cancer cells.
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.
Kim
In Young
IY
Department of Toxicology, National Institute of Toxicological Research, Seoul, Korea.
Han
Soon Young
SY
Kang
Tae Seok
TS
Lee
Byung Mu
BM
Choi
Kwang Sik
KS
Moon
Hyun Ju
HJ
Kim
Tae Sung
TS
Kang
Il Hyun
IH
Kwack
Seung Jun
SJ
Moon
Aree
A
Ahn
Mee Young
MY
Kim
Hyung Sik
HS
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D009570:Nitriles / Q000633:toxicity*; D026023:Permethrin / Q000633:toxicity*; D011374:Progesterone; D011722:Pyrethrins / Q000633:toxicity*; D011980:Receptors, Progesterone / Q000378:metabolism
D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D011980:Receptors, Progesterone; D011374:Progesterone; D026023:Permethrin; D000469:Alkaline Phosphatase; C017690:fenvalerate