Antitumor Activity of Emodin against Pancreatic Cancer Depends on Its Dual Role: Promotion of Apoptosis and Suppression of Angiogenesis

Lin, Sensen; Wei, Wei‐Tian; Chen, Hui; Chen, Kangjie; Tong, Hongfei; Wang, Zhaohong; Ni, Zhonglin; Liu, Haibin; Guo, Hong-Chun; Liu, Dian-Lei

doi:10.1371/journal.pone.0042146

Cited by 72 publications

(59 citation statements)

References 27 publications

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“…Notably, emodin inhibited epithelial-mesenchymal transition, suggesting that emodin may have anticancer effects (18). Additionally, a study demonstrated that emodin enhanced anticancer effects when used in combination with gemcitabine (19). However, little is known about the effects of emodin in breast cancer cells.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…To analyze cell invasion, the upper surface of a filter membrane in the upper compartment of a Transwell was coated with 30 µg Matrigel. Cells (1x10 5 ) suspended in 200 µl of serum-free medium were seeded onto the upper compartment of the Transwell and the lower chambers were filled with medium containing 10% FCS and various concentrations of emodin. After 24 h, the cells remaining in the upper chamber were removed and cells on the undersurface of the filters were fixed with 70% ethanol followed by staining with 0.5% Coomassie brilliant blue for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…1A), an active monomer extracted from Rheum, Polygonum, Buckthorn and Senna, has been shown to be active against pancreatic (5,6), lung (7,8), breast (9,10), liver (11), prostate (12,13), ovarian (14), cervical (15), colon (16), gallbladder (17) and human tongue cancer SCC-4 cells (18,19). Moreover, it has been reported that emodin induces apoptosis of human breast cancer MCF-7 (20) and MDA-MB-453 cells (21).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo

et al. 2014

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Abstract. In breast cancer, metastasis is the main reason for patient mortality. In the present study, we used breast cancer MDA-MB-231 cells and a mouse xenograft model to demonstrate the effect of emodin on the migration, invasion and metastasis of human breast cancer MDA-MB-231 cells and the related mechanisms. In vitro, wound healing and Transwell assays showed that emodin dose-dependently inhibited the migration and invasion of MDA-MB-231 cells. Enzyme-linked immunosorbent assay (ELISA) showed that emodin decreased the secretion of MMP-2 and MMP-9. Western blot analysis showed that emodin downregulated the expression levels of MMP-2, MMP-9, uPA and uPAR as well as p38 inhibitor SB203580 and ERK inhibitor PD980559, even though TIMP-1 and TIMP-2 were not obviously changed in the MDA-MB-231 cells. Furthermore, emodin inhibited the activity of p38 and ERK1/2 in the MDA-MB-231 cells. In vivo, emodin inhibited lung metastasis in mice bearing the breast cancer MDA-MB-231 xenografts with no obvious changes in body weight, liver and kidney functions. These results indicated that emodin inhibited the lung metastasis of human breast cancer in a mouse xenograft model, and inhibited the invasion of MDA-MB-231 cells associated with the downregulation of MMP-2, MMP-9, uPA and uPAR expression as well as decreased activity of p38 and ERK.

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“…Down regulation of VEGF-A gene expression by emodin can probably be the result of inhibitory effect of emodin on NF-KB which is required for expression of VEGF-A gene (25).…”

Section: Discussionmentioning

confidence: 99%

Effect of Emodin on Expression of VEGF-A and VEGFR_2 Genes in Human Breast Carcinoma MCF-7 Cell

et al. 2017

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Background: Tumor angiogenesis is an important procedure for the tumor development as it confirms oxygen and nutrients source to increase cells through the expansion of new blood vessels, potentially causing cancer development and metastasis. Emodin, a tyrosine kinase inhibitor, is an innate anthraquinone derivative found in the roots and rhizomes of several plants. Pharmacological studies have revealed that emodin displays various biological roles, such as anti-inflammatory, antibacterial and anticancer action. Studies have confirmed that emodin prevents cell growth in some types of cancer cells. Therefore, inhibition of angiogenesis is a new strategy for cancer treatment.

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Antitumor Activity of Emodin against Pancreatic Cancer Depends on Its Dual Role: Promotion of Apoptosis and Suppression of Angiogenesis

Cited by 72 publications

References 27 publications

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

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

Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo

Effect of Emodin on Expression of VEGF-A and VEGFR_2 Genes in Human Breast Carcinoma MCF-7 Cell

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