Kim In Young, Han Soon Young, Kang Tae Seok, Lee Byung Mu, Choi Kwang Sik, Moon Hyun Ju, Kim Tae Sung, Kang Il Hyun, Kwack Seung Jun, Moon Aree, Ahn Mee Young, Kim Hyung Sik
Department of Toxicology, National Institute of Toxicological Research, Seoul, Korea.
J Toxicol Environ Health A. 2005 Dec 10;68(23-24):2175-86. doi: 10.1080/15287390500180523.
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.
拟除虫菊酯类杀虫剂通过刺激MCF - 7细胞增殖以及诱导培养的石川细胞中碱性磷酸酶（AlkP）的活性，表现出微弱的雌激素活性。此前有报道称，氰戊菊酯和氯菊酯能显著抑制17β - 雌二醇诱导的MCF - 7 BUS细胞增殖。尽管某些拟除虫菊酯类杀虫剂具有雌激素或抗雌激素活性，但尚不清楚拟除虫菊酯类杀虫剂是作为孕激素激动剂还是拮抗剂起作用。因此，本研究的目的是评估氰戊菊酯和氯菊酯对T47D细胞中作为孕激素特异性反应的AlkP活性的影响。在本研究中，随着孕酮的添加，AlkP活性的刺激呈浓度依赖性，在浓度为1×10⁻⁸ M时观察到最大活性。氰戊菊酯（1×10⁻⁶ M）和氯菊酯（1×10⁻⁶ M）均未刺激AlkP活性，但在氰戊菊酯和氯菊酯浓度均为1×10⁻⁶ M时，孕酮（1×10⁻⁸ M）诱导的AlkP活性分别受到显著抑制。研究了T47D细胞胞质蛋白中的孕激素受体（PR）水平，以确定细胞PR表达与AlkP活性之间的关系。与AlkP活性相似，与对照组相比，孕酮（1×10⁻⁸ M）显著提高了PR蛋白水平。然而，单独用氰戊菊酯和氯菊酯培养的T47D细胞中PR蛋白水平未受影响，而氰戊菊酯和氯菊酯显著降低了孕酮诱导的PR蛋白水平。我们的数据表明，氰戊菊酯和氯菊酯在T47D人乳腺癌细胞中表现出抗孕激素活性。
