Ying Tang1, Qi Fang1, Daohua Shi2, Peiguang Niu1, Yaoyao Chen1, Jie Deng1. 1. Department of Pharmacy, Fujian Provincial Maternal and Child Health Hospital, Fuzhou, Fujian 350001, China. 2. Department of Pharmacy, Fujian Provincial Maternal and Child Health Hospital, Fuzhou, Fujian 350001, China. Electronic address: shidh@yeah.net.
Abstract
AIMS: Cardamonin has previously demonstrated that it had an antiproliferative effect on vascular smooth muscle cells by inhibiting the activity of mammalian target of rapamycin (mTOR). The antiproliferative effect and the possible mechanism of combining with mTOR of cardamonin were investigated on A549 cells. MAIN METHODS: Cell proliferation, cell cycle and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. mTOR and 12 kDa FK506 binding protein (FKBP12) were transfected into A549 cells by Lipofectamine. Western blots were used to examine the mTOR expressions and its activities, and the expressions of 70 kDa ribosomal S6 kinase (p70S6K), FKBP12 and Interleukin-2 (IL-2), respectively. KEY FINDINGS: Treated with cardamonin, the proliferation of A549 cells was inhibited. Meanwhile, cell cycle was blocked and DNA synthesis was decreased whereas cell apoptosis was promoted, and the activation of mTOR and p70S6K was decreased by cardamonin. Transfected with mTOR or FKBP12, proliferation of A549 cells was increased. Rapamycin had a similar degree of effect on antiproliferation of both transfected cells. However, the antiproliferative effect of cardamonin on mTOR transfected cells was stronger than that on FKBP12 transfected cells. Both rapamycin and cardamonin decreased the phosphorylation of mTOR and p70S6K in two kinds of transfected cells. Cardamonin had no effect on the expression of FKBP12 and IL-2, whereas the expressions were decreased by rapamycin. SIGNIFICANCE: Cardamonin inhibited proliferation and induced apoptosis of A549 cells via mTOR. It might directly interact with mTOR independently of binding with FKBP12.
AIMS: Cardamonin has previously demonstrated that it had an antiproliferative effect on vascular smooth muscle cells by inhibiting the activity of mammalian target of rapamycin (mTOR). The antiproliferative effect and the possible mechanism of combining with mTOR of cardamonin were investigated on A549 cells. MAIN METHODS: Cell proliferation, cell cycle and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. mTOR and 12 kDa FK506 binding protein (FKBP12) were transfected into A549 cells by Lipofectamine. Western blots were used to examine the mTOR expressions and its activities, and the expressions of 70 kDa ribosomal S6 kinase (p70S6K), FKBP12 and Interleukin-2 (IL-2), respectively. KEY FINDINGS: Treated with cardamonin, the proliferation of A549 cells was inhibited. Meanwhile, cell cycle was blocked and DNA synthesis was decreased whereas cell apoptosis was promoted, and the activation of mTOR and p70S6K was decreased by cardamonin. Transfected with mTOR or FKBP12, proliferation of A549 cells was increased. Rapamycin had a similar degree of effect on antiproliferation of both transfected cells. However, the antiproliferative effect of cardamonin on mTOR transfected cells was stronger than that on FKBP12 transfected cells. Both rapamycin and cardamonin decreased the phosphorylation of mTOR and p70S6K in two kinds of transfected cells. Cardamonin had no effect on the expression of FKBP12 and IL-2, whereas the expressions were decreased by rapamycin. SIGNIFICANCE: Cardamonin inhibited proliferation and induced apoptosis of A549 cells via mTOR. It might directly interact with mTOR independently of binding with FKBP12.
Authors: Tianyi Wang; Kaiqi Long; Yang Zhou; Xiaoding Jiang; Jinzhao Liu; John H C Fong; Alan S L Wong; Wai-Lung Ng; Weiping Wang Journal: ACS Pharmacol Transl Sci Date: 2022-02-08
Authors: Eun Ji Kim; Hyun Ji Kim; Mi Kyung Park; Gyeung Jin Kang; Hyun Jung Byun; Ho Lee; Chang Hoon Lee Journal: Biomol Ther (Seoul) Date: 2015-03-01 Impact factor: 4.634