Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway

Xie, Mei‐Juan; Ma, Yihua; Ma, Lin; Wang, Yan; Wang, Haizhen; Xing, Yingying; Xi, Tao; Lu, Yuanyuan

doi:10.7314/apjcp.2014.15.13.5201

Cited by 45 publications

(29 citation statements)

References 27 publications

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“…Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an anthraquinone found in certain plants and has been evaluated for its antiproliferative and apoptotic activities in various cancer cell lines, including breast (10), liver (11), lung (12), prostate (13) and cervical cancer (14), leukemia (15) and colon cancer (16). Emodin has an anticancer effect based on the suppression of migration, invasion and angiogenesis (17,18).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

Lee

Young

et al. 2017

Molecular Medicine Reports

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Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit-8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining. FASN activity was measured by monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength of 340 nm, and intracellular free fatty acid levels were detected using a Free Fatty Acid Quantification kit. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect target gene and protein expression. The present study was performed to investigate whether the gene expression of FASN and its enzymatic activity are regulated by emodin in a human colon cancer cell line. Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU-C5 cells. Emodin significantly downregulated the protein expression of FASN in HCT116 cells, which was caused by protein degradation due to elevated protein ubiquitination. Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis in a dose- and time-dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect on these activities. Palmitate, the final product of the FASN reaction, rescued emodin-induced viability and apoptosis. In addition, emodin altered FASN-involved signaling pathways, including phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinases/extracellular signal-regulated kinases 1/2. These results suggested that emodin-regulated cell growth and apoptosis were mediated by inhibiting FASN and provide a molecular basis for colon cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

Lee

Young

et al. 2017

Molecular Medicine Reports

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“…24. In recent decades, increased attention was focused on anticancer activities of emodin since studies have reported that it exhibits antiproliferative and apoptosis-inducing effects in a number of human cancers such as colon, cervical and gastric cancer (9)(10)(11). It may also suppress migration and metastasis of cancer such as breast cancer and HCC (12,13).…”

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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“…Molecular mechanisms involved include tyrosine kinases [3,31], casein kinase II [1], protein kinase C [47], AKT/mTOR [1,28,62], NF-κB [1,67,68], HIF-1α [1], STAT3 [1,59], p53 [1,21,23,32,54], Wnt signaling [69], Bcl-2/Bax [21,26,28], mitochondria [38,44,45,49,51,57,63,64], oxidative stress [21,23,32,49,57,61,70], and endoplasmic reticulum stress [38].…”

Section: Introductionmentioning

confidence: 99%

Triggering of Erythrocyte Cell Membrane Scrambling by Emodin

Mischitelli

Jèmaà²,

Almasry³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The natural anthraquinone derivative emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a component of several Chinese medicinal herbal preparations utilized for more than 2000 years. The substance has been used against diverse disorders including malignancy, inflammation and microbial infection. The substance is effective in part by triggering suicidal death or apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the triggering of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), oxidative stress and ceramide. The present study aimed to test, whether emodin induces eryptosis and, if so, to elucidate underlying cellular mechanisms. Methods: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Results: Exposure of human erythrocytes for 48 hours to emodin (≥ 10 µM) significantly increased the percentage of annexin-V-binding cells, and at higher concentrations (≥ 50 µM) significantly increased forward scatter. Emodin significantly increased Fluo3-fluorescence (≥ 10 µM), DCFDA fluorescence (75 µM) and ceramide abundance (75 µM). The effect of emodin on annexin-V-binding was significantly blunted but not abolished by removal of extracellular Ca²⁺. Conclusions: Emodin triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to stimulation of Ca²⁺ entry and paralleled by oxidative stress and ceramide appearance at the erythroctye surface.

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Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway

Cited by 45 publications

References 27 publications

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

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

Triggering of Erythrocyte Cell Membrane Scrambling by Emodin

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