Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c

Ma, Liang; Li, Wusheng

doi:10.3892/etm.2014.1900

Cited by 46 publications

(29 citation statements)

References 18 publications

(16 reference statements)

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“…These observations demonstrate that emodin-induced apoptosis of Bcap-37 and ZR-75-30 cells was triggered by the downregulation of Bcl-2 and the upregulation of Bax. Previous studies have demonstrated that the mitochondrial membrane potential stimulates the opening of the mitochondrial membrane, resulting in the release of cytochrome c into the cytoplasm, caspase activation and degradation of key intracellular proteins, which leads to apoptosis (31,32).…”

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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“…Bcl-2 and Bax proteins are members of the Bcl family of proteins (13,14). A number of studies have reported that the Bcl-2 family proteins participate in AD, and are associated with cell apoptosis (15,16).…”

Section: B Amentioning

confidence: 99%

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease

Jia¹,

Wang²,

Zhang³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. In previous years, increasing evidence has indicated that paraptosis and mitochondrial-mediated apoptosis may be associated with Alzheimer's disease (AD). However, the association between paraptosis and mitochondrial-mediated apoptosis, and the pathological processes underlying AD, remain elusive. In the present study, the β-amyloid precursor protein gene, and the gene mutations PS1M146L and L286V, were transfected to an SH-SY5Y cell line to establish an AD cell model. Subsequently, an MTT assay was used to examine the cell viability of the AD cell model, while a TUNEL assay was employed to observe the number of positively stained apoptotic cells. Cytoplasmic vacuolization was examined using light microscopy and images were photographed. Furthermore, western blot analysis was utilized to detect the expression of golden biomarkers of the mitochondrial pathway, including Bcl-2 and Bax. The paraptosis inhibitor, cycloheximide, was selected to treat the AD model cells in order to observe the association between paraptosis and mitochondrial-mediated apoptosis. The results indicated that the decrease in the cell viability of the AD cells was initiated at 24 h, as compared with the normal cells (P<0.05). TUNEL-positive stained cells were observed at 48 h, which was later compared with the cell death initiation. In addition, examination of cytoplasmic vacuolization using microscopy indicated that there were a small number of paraptosis cells present at 24 h. The expression levels of Bcl-2 was significantly decreased, while Bax was significantly increased at 48 h. Furthermore, cycloheximide treatment was demonstrated to significantly increase Bcl-2 expression, while decreasing Bax expression (P>0.05). In conclusion, the occurrence of paraptosis was demonstrated in the early pathological stages of AD, which may subsequently damage the mitochondria and trigger mitochondrial pathway-mediated apoptosis. Thus, paraptosis may trigger programmed cell death directly, or indirectly through the regulation of Bcl-2 and Bax protein expression.

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“…Among these, many of the medicines derive from Traditional Chinese Medicine (TCM) and have been confirmed to be effective in the treatment of a number of tumors via targeting and regulating multiple molecular pathways (5,6). Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L, which is a plant widely used in Chinese medicine as a laxative for thousands of years (7,8). The molecular formula of emodin is C 15 H 10 O 5 and its molecular weight is 270.…”

Section: Introductionmentioning

confidence: 99%

Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo

et al. 2016

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Abstract. Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L and many studies have reported that it exhibits anticancer effects in a number of human tumors. However, there is little information demonstrating the possible effects of emodin on the proliferation and apoptosis of hepatocellular carcinoma (HCC). In the present study, we show that emodin may inhibit the proliferation of SMMC-7721 cells in a dose-and time-dependent manner and induced apoptosis of cells in a concentration-dependent manner after treatment for 24 h. Moreover, we further discovered that the possible molecular mechanisms involved may relate to the mitogenactivated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Emodin may induce the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38 while mildly suppressed the expression of p-c-Jun-N-terminal kinase (p-JNK). However, emodin did not affect the expression of the total (t)-ERK, t-p38 or t-JNK. Furthermore, emodin also suppressed the activation of p-AKT, but not the t-AKT. In vivo, we found that emodin suppressed tumor growth in experimental mice without an obvious change in body weight, which may work through the antiproliferation and apoptosis inducing effects. Moreover, emodin improves the liver and kidney function in mice, revealing that emodin may improve the life quality of the mice with implanted tumors. In conclusion, the above findings indicate that emodin may be a potentially effective and safe drug to induce apoptosis of HCC.

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Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c

Cited by 46 publications

References 18 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

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease

Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo

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