Emodin induces apoptosis through caspase 3-dependent pathway in HK-2 cells

Wang, Cuifen; Wu, Xudong; Chen, Min; Duan, Weigang; Sun, Lixin; Yan, Ming; Zhang, Luyong

doi:10.1016/j.tox.2006.11.064

Cited by 85 publications

(59 citation statements)

References 21 publications

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“…Emodin inhibits tumor cell growth and sensitizes tumor cells to chemotherapy through the inhibition of tyrosine kinase activation (Wang et al, 2007a). In the present study, we observed 30 M emodin affecting p-JNK and p-p38 after 12 to 24 h of treatment, but after 48 and 72 h of incubation, p-JNK and p-p38 levels were increased.…”

supporting

confidence: 52%

“…This compound also triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, mitochondrial cytochrome c release, and caspase activation, leading to apoptosis (Su et al, 2005). Emodin induces apoptosis in human proximal tubular epithelial HK-2 cells through the caspase-3-dependent pathway (Wang et al, 2007a) and increases arsenic trioxide interferon-␥-induced cell death of HTLV-Itransformed cells by ROS generation and inhibition of AKT and AP-1 (Brown et al, 2007).…”

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confidence: 99%

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Emodin Has Cytotoxic and Protective Effects in Rat C6 Glioma Cells: Roles of Mdr1a and Nuclear Factor κB in Cell Survival

Kuo¹,

Yang²,

Meng³

et al. 2009

J Pharmacol Exp Ther

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ABSTRACT1,3,8-Trihydroxy-6-methylanthaquinone (emodin) is recognized as an antiproliferative compound. In the present study, however, we show that emodin has both toxic and survival effects in glioma cells and that the survival effects involve Mdr1a. Emodin inhibited the proliferation and induced apoptosis of C6 cells in a 12-h treatment, but C6 cells survived a 72-h drug treatment, indicating resistance to emodin. Emodin-induced apoptosis was reduced by inhibition of the expression and activation of apoptosis-associated proteins including p53, Bax, Bcl-2, Fas, and caspase-3. C6 cells could express antioxidant proteins (superoxide dismutase and catalase) to decrease reactive oxygen species-induced cytotoxicity of emodin and overexpress multidrug resistance genes (Mdr1a, MRP2, MRP3, and MRP6) to decrease the intracellular accumulation of emodin. Electrophoretic mobility shift analysis showed that emodin decreased nuclear factor B (NF-B) expression in 24 h of treatment, but in 48 h, emodin increased NF-B activity. A confocal microscope showed that emodin induced NF-B translocation from cytoplasm to nuclei. C6 cells would activate the mitogen-activated protein kinase survival pathway and express the DNA repair gene (MGMT) and associated proteins (PARP and XRCC1) to recover the cell activity. C6 cells also expressed GRP78 to decrease emodin-induced endoplasmic reticulum (ER) stress that would cause apoptosis in C6 cells, and GRP78 inhibited the expression of GADD153 to enhance the expression of Bcl-2 that could balance the ER-and mitochondria-induced apoptosis of C6 cells.

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supporting

confidence: 52%

mentioning

confidence: 99%

Emodin Has Cytotoxic and Protective Effects in Rat C6 Glioma Cells: Roles of Mdr1a and Nuclear Factor κB in Cell Survival

Kuo¹,

Yang²,

Meng³

et al. 2009

J Pharmacol Exp Ther

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“…Emodin is also observed naturally in a number of widely used Chinese medicinal herbs, including Rheum officinale (8) and Polygonam cuspidatummedicine (9). It has been widely studied for its antibacterial, diuretic, immuno suppressive, anti-inflammatory and vaso relaxant effects.…”

Section: Introductionmentioning

confidence: 99%

Emodin induces apoptosis of human breast cancer cells by modulating the expression of apoptosis-related genes

Zhang

Hou

et al. 2015

Oncology Letters

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Abstract. The aim of this study was to investigate the effects of emodin on the proliferation of human breast cancer cells . Cell viability following emodin treatment was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of emodin on apoptosis were determined by flow cytometry using Annexin V-fluorescein isothiocyanate and propidium iodide staining. Quantitative polymerase chain reaction and western blot analysis were used to determine changes in the expression of apoptotic genes and protein, respectively. The effect of emodin on the invasiveness of breast cancer cells was evaluated by Matrigel invasion assay. Treatment of breast cancer cells Bcap-37 and ZR-75-30 with emodin was observed to inhibit the growth and induced apoptosis in a time-and dose-dependent manner. Emodin reduced the level of Bcl-2 and increased levels of cleaved caspase-3, PARP, p53 and Bax. These findings indicate that emodin induces growth inhibition and apoptosis in human breast cancer cells. Emodin may be a potential therapeutic agent for the treatment of breast cancer. IntroductionBreast cancer is a common malignant tumor and accounts for the majority of cancer mortality in females (1). Breast cancer has an estimated incidence of 1,676,633 and had an estimated mortality rate of 521,817 in 2012 worldwide (2). In China, there has been an increasing incidence of breast cancer in recent decades (3). In 2012, it was estimated that ~48,000 females would succumb to breast cancer. To date, chemotherapy has been the mainstay for the treatment of breast cancer. However, the side effects and drug resistance associated with chemotherapy have limited its effectiveness for the treatment of breast cancer (4,5). A number of natural extractions have demonstrated a wide range of biological activity and low toxicity in animal models, and have been considered as an alternative method of breast cancer treatment (6,7).Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a biologically active anthraquinone identified in the roots and bark of a number of plants. Emodin is also observed naturally in a number of widely used Chinese medicinal herbs, including Rheum officinale (8) and Polygonam cuspidatummedicine (9). It has been widely studied for its antibacterial, diuretic, immuno suppressive, anti-inflammatory and vaso relaxant effects. It has been reported that emodin induces apoptosis of several types of human cancer cells (10-13) by modulating various signaling pathways. However, the biological mechanisms by which emodin induces cytotoxicity remain largely unknown. Furthermore, the biological effects of emodin on breast cancer cells remain to be determined.In this study, the effects of emodin on the proliferation and apoptosis of breast cancer cells were assessed. In addition, the mechanism by which emodin mediates these biological effects was elucidated. We demonstrated that emodin inhibited the proliferation and induced apoptosis of Bcap-37 and ZR-75-30 breast cancer cells. These observations suggest that emodi...

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“…Moreover, emodin increased the activation of caspase-3 in human chronic myelocytic leukemia K562 cell lines. In another research, emodin-induced HK-2 cell apoptosis through the activation of caspase 3 in HK2 cells (15,22,27).…”

Section: Discussionmentioning

confidence: 94%