Evodiamine induces apoptosis and inhibits metastasis in MDA-MB-231 human breast cancer cells in vitro and in vivo

Du, Jing; Wang, Xiufeng; Zhou, Qian-Mei; Zhang, Tianling; Lu, Yi‐Yu; Zhang, Hui; Su, Shi‐Bing

doi:10.3892/or.2013.2498

Cited by 67 publications

(57 citation statements)

References 35 publications

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“…In the present study, it was shown that PDGF-BB stimulation significantly increased the levels of phosphorylated p38 MAPK and Erk1/2 in VSMCs, which was inhibited by evodiamine treatment. These findings were in accordance with previous studies involving tumor cells, and suggested that the inhibition of mitogenesis and p-38/p-Erk activity may serve as the molecular basis for the functions of evodiamine (21,27,28). However, the regulation of p38 and Erk activity by evodiamine is cell type-dependent and may be negative or positive.…”

Section: Discussionsupporting

confidence: 93%

“…Therefore, the observation that PDGF-BB increased and evodiamine decreased the expression of p21 in the present study was not unusual. Of note, the inhibitory effects of evodiamine on cell cycle progression have been previously observed in various human tumor cell lines, including small-cell lung cancer cells (20), gastric cancer cells (11), breast cancer cells (21), gastric adenocarcinoma cells (22) and cervical carcinoma HeLa cells (23), and are considered to be important in the antitumor action of evodiamine. The data obtained in the present study extends the current recognition of evodiamine, and suggested that the regulation of cell cycle progression by evodiamine may be general and function in a broader range of cell types, including tumor cells and vascular cells.…”

Section: Discussionmentioning

confidence: 97%

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Evodiamine inhibits PDGF-BB-induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Ge¹,

Chen²,

Liu³

et al. 2016

Molecular Medicine Reports

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Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in-stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet-derived growth factor-BB (PDGF-BB) stimulation. It was found that evodiamine inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle-promoting cyclin proteins and cyclin-dependent kinases. In addition, evodiamine attenuated the PDGF-BB-induced phosphorylation of mitogen-activated protein kinases p38 and extracellular signal-regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Evodiamine inhibits PDGF-BB-induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Ge¹,

Chen²,

Liu³

et al. 2016

Molecular Medicine Reports

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“…Du et al (2013) reported that EVO-induced apoptosis was enhanced by its combination with the ERK inhibitor, PD98059, or the p38 MAPK inhibitor, SB203580 [30]. The relationship of MAPK to EVO-induced apoptosis and cell cycle arrest is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Activation of JNK Contributes to Evodiamine-Induced Apoptosis and G2/M Arrest in Human Colorectal Carcinoma Cells: A Structure-Activity Study of Evodiamine

Chien

Shen

et al. 2014

PLoS ONE

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Evodiamine (EVO; 8,13,13b,14-tetrahydro-14-methylindolo[2′3′-3,4]pyrido[2,1-b]quinazolin-5-[7H]-one derived from the traditional herbal medicine Evodia rutaecarpa was reported to possess anticancer activity; however, the anticancer mechanism is still unclear. In this study, we investigated the anticancer effects of EVO on human colon COLO205 and HT-29 cells and their potential mechanisms. MTT and lactate dehydrogenase (LDH) release assays showed that the viability of COLOL205 and HT-29 cells was inhibited by EVO at various concentrations in accordance with increases in the percentage of apoptotic cells and cleavage of caspase-3 and poly(ADP ribose) polymerase (PARP) proteins. Disruption of the mitochondrial membrane potential by EVO was accompanied by increased Bax, caspase-9 protein cleavage, and cytochrome (Cyt) c protein translocation in COLO205 and HT-29 cells. Application of the antioxidant N-acetyl-L-cysteine (NAC) inhibited H2O2-induced reactive oxygen species (ROS) production and apoptosis, but did not affect EVO-induced apoptosis of COLO205 or HT-29 cells. Significant increases in the G2/M ratio and cyclinB1/cdc25c protein expression by EVO were respectively identified in colon carcinoma cells via a flow cytometric analysis and Western blotting. Induction of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) protein phosphorylation was detected in EVO-treated cells, and the JNK inhibitor, SP600125, but not the ERK inhibitor, U0126, inhibited EVO-induced phosphorylated JNK protein expression, apoptosis, and G2/M arrest of colon carcinoma cells. Data of the structure-activity analysis showed that EVO-related chemicals containing an alkyl group at position 14 were able to induce apoptosis, G2/M arrest associated with increased DNA ladder formation, cleavage of caspase-3 and PARP, and elevated cycB1 and cdc25c protein expressions in COLO205 and HT-29 cells. Evidence supporting JNK activation leading to EVO-induced apoptosis and G2/M arrest in colon carcinoma cells is provided, and alkylation at position 14 of EVO is a critical substitution for treatment of colonic cancer.

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“…Both ERK and p38 are important members of the MAPK pathways for cancer invasion and metastasis, which are involved in the regulation of MMP-2, MMP-9 and uPA in breast cancer (43). Previous research has found that certain natural products can inhibit breast cancer metastasis by downregulated the expressions of MMP-2, MMP-9 and uPA through inhibition of the p38 signaling pathway (44). In the present study, emodin as well as SB203580, a p38-specific inhibitor and PD98059, an ERK specific inhibitor, decreased the activation of p38 and ERK1/2 and the expression levels of MMP-2, MMP-9 and uPA, but the combination treatment of emodin and SB203580 or PD98059 did not obviously alter these inhibitory effects in MDA-MB-231 cells (Figs.…”

Section: Discussionmentioning

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

Self Cite

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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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Evodiamine induces apoptosis and inhibits metastasis in MDA-MB-231 human breast cancer cells in vitro and in vivo

Cited by 67 publications

References 35 publications

Evodiamine inhibits PDGF-BB-induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Evodiamine inhibits PDGF-BB-induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Activation of JNK Contributes to Evodiamine-Induced Apoptosis and G2/M Arrest in Human Colorectal Carcinoma Cells: A Structure-Activity Study of Evodiamine

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

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