Evodiamine, a constituent of <i>Evodiae Fructus</i>, induces anti‐proliferating effects in tumor cells

Fei, Xiao Fang; Wang, Ben Xiang; Li, Tei Jin; Tashiro, Shin‐ichi; Minami, Manabu; Xing, De Jun; Ikejima, Takashi

doi:10.1111/j.1349-7006.2003.tb01358.x

Cited by 124 publications

(89 citation statements)

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“…2). These results are in line with previous reports that evodiamine-induced cell death is associated with apoptosis in different cancer cell types such as breast (8), thyroid (9), liver (10), prostate (11-14), leukemic T-lymphocyte (5,15), melanoma (6,(16)(17)(18), cervical (19,20), colon (21)(22)(23)(24), colorectal (25) and lung cancer cells (26).…”

Section: Resultssupporting

confidence: 92%

“…Evodiamine is a naturally occurring quinolone alkaloid found in the fruit of Evodia rutaecarpa. The data of several studies concerning its cytotoxic activity in cancer cells demonstrated that evodiamine inhibited the growth of a wide variety of tumor cells, including breast (8), thyroid (9), liver (10), prostate (11)(12)(13)(14), leukemic T-lymphocyte (5,15), melanoma (6,(16)(17)(18) cervical (19,20), colon (21)(22)(23)(24), colorectal (25) and lung cells (26) through induction of apoptosis, regulation of cell cycle and reduction of invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy

2012

Oncol Rep

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Abstract. Evodiamine, an alkaloid isolated from Evodia rutaecarpa, possesses potent anticancer activity. Although many reports have elucidated the cytotoxic effects of evodiamine in a variety of cancer cells, little is known about the mechanism of evodiamine-induced cytotoxic activity in gastric cancer cells. To date, no report has addressed the synchronized role of autophagy and apoptosis in evodiamineinduced cytotoxic activity. This study was conducted to investigate the synchronized role of autophagy and apoptosis in evodiamine-induced cytotoxic activity on SGC-7901 human gastric adenocarcinoma cells and further to elucidate the underlying molecular mechanisms. The MTT assay was used to examine the cytotoxicity of evodiamine against SGC-7901 gastric adenocarcinoma cells. The effects of evodiamine on the cell cycle and apoptosis were measured by flow cytometry and cellular morphology was observed under a phase contrast microscope. Acridine orange (AO) staining was used to detect autophagy. The expression levels of Bcl-2 and Bax were detected by Western blotting. The expression level of Beclin-1 in SGC-7901 cells was monitored by reverse transcription-polymerase chain reaction (RT-PCR). Here, we found that evodiamine significantly inhibited the proliferation of SGC-7901 cells and induced G2/M phase cell cycle arrest. Furthermore, both autophagy and apoptosis were activated during the evodiamine-induced death of SGC-7901 cells. Evodiamine-induced autophagy is partially involved in the death of SGC-7901 cells which was confirmed by using the autophagy inhibitor 3-methyladenine (3-MA). Additionally, Beclin-1 is involved in evodiamine-induced autophagy and the pro-apoptotic mechanisms of evodiamine may be associated with down-regulation of Bcl-2 and up-regulation of Bax expression. The inhibitory effects on SGC-7901 cells were associated with apoptosis, autophagy and cell cycle arrest at the G2/M phase in a dose-dependent manner. These results suggest that evodiamine is an effective natural compound for the treatment of gastric cancer and may represent a candidate for in vivo studies of monotherapies or combined antitumor therapies.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy

2012

Oncol Rep

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“…9A), has a different three-dimensional structure than evodiamine, and cannot inhibit cell proliferation or invasion (6,9). We investigated whether rutaecarpine affects NF-B activation.…”

Section: Evodiamine Represses Tnf-induced Nf-b-dependent Genementioning

confidence: 99%

“…Evodiamine 1 (see Fig. 1) has recently been shown to suppress the proliferation of a wide variety of tumor cells, including prostate cancer cells (4), leukemic T-lymphocytes (5), monocytic leukemia cells (6), melanoma cells (6,7), cervical cancer cells (6), and mouse fibrosarcoma cells (6), but it apparently has no toxic effects against normal peripheral blood mononuclear cells (6). 1 The abbreviations used and trivial name are: evodiamine, 8,13,13b14-tetrahydro-14-methlindolo[2Ј3Ј: 3,4]pyrido [2,1-b]quinazolin-5-[7H]-one; NF-B, nuclear factor-B; IB, inhibitory subunit of NF-B; IKK, IB␣ kinase; TNF, tumor necrosis factor; TNFR, TNF receptor; TRADD, TNFR-associated death domain; NIK, NF-B-inducing kinase; IL, interleukin; SEAP, secretory alkaline phosphatase; PMA, phorbol 12-myristate 13-acetate; TUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling; IAP, inhibitor-of-apoptosis protein; XIAP, X chromosome-linked IAP; FLIP, Fas-associated death domain protein-like IL-1␤-converting enzyme-inhibitory protein; COX, cyclooxygenase; MMP, matrix metalloproteinase; TRAF, TNF receptor-associated factor, PBS, phosphate-buffered saline; ICAM, intercellular adhesion molecule; MDR, multidrug resistance protein; NO, nitric oxide; FBS, fetal bovine serum; JNK, c-Jun NH 2 -terminal kinase; MAPK, mitogen-activated protein kinase; PARP, poly(ADP-ribose) polymerase; EMSA, electrophoretic mobility shift assay; GST, glutathione S-transferase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.…”

mentioning

confidence: 99%

Evodiamine Abolishes Constitutive and Inducible NF-κB Activation by Inhibiting IκBα Kinase Activation, Thereby Suppressing NF-κB-regulated Antiapoptotic and Metastatic Gene Expression, Up-regulating Apoptosis, and Inhibiting Invasion

Takada

Kobayashi

Aggarwal

2005

Journal of Biological Chemistry

172

102

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Evodiamine, an alkaloidal component extracted from the fruit of Evodiae fructus (Evodia rutaecarpa Benth., Rutaceae), exhibits antiproliferative, antimetastatic, and apoptotic activities through a poorly defined mechanism. Because several genes that regulate cellular proliferation, carcinogenesis, metastasis, and survival are regulated by nuclear factor-B (NF-B), we postulated that evodiamine mediates its activity by modulating NF-B activation. In the present study, we investigated the effect of evodiamine on NF-B and NF-B-regulated gene expression activated by various carcinogens. We demonstrate that evodiamine was a highly potent inhibitor of NF-B activation, and it abrogated both inducible and constitutive NF-B activation. The inhibition corresponded with the sequential suppression of IB␣ kinase activity, IB␣ phosphorylation, IB␣ degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation. Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation.

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“…Evodiamine (evo) is a quinazolinocarboline alkaloid extracted from the fruit of Wu-Zhu-Yu (Evodiae fructus; Evodia rutaecarpa Benth, Rutaceae), which has been used in traditional Chinese medicine for the treatment of gastrointestinal disorders, headache and hypertension. [23][24][25] It has recently been reported that evo exerts antiobesity effects through the stimulation of an extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. 26 Therefore, it was interesting to assess the effects of evo alone and in combination with rosi on adipocyte differentiation in vitro and obesity related to diabetes in vivo.…”

Section: -13mentioning

confidence: 99%

Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes

Bak

Kim

et al. 2009

Int J Obes

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Objective: Evodiamine (evo) has been shown to exert anti-inflammatory, antinociceptive and anticancer effects. In this study, we investigated the effects of evo alone and in combination with rosiglitazone (rosi) on in vitro adipocyte differentiation and in vivo obesity related to diabetes. Methods: Adipocyte differentiation was investigated in vitro using 3T3-L1 and C3H10T1/2 cells. To determine the degree of differentiation, Oil Red O staining and reverse transcription-PCR were carried out. Four groups of db/db mice were treated intraperitoneally once per day with vehicle, evo, rosi and evo þ rosi. The mice were killed after 14 days and the blood, liver and adipose tissue were analyzed. Results: The presence of evo or evo combined with rosi during adipogenic induction has been shown to inhibit adipocyte differentiation to a significant degree, particularly at the commitment and early induction stages. The evo and evo þ rosi groups of db/db mice evidenced significant reductions in body weight gain. The ratio of epididymal white adipocyte tissue weight to body weight of the evo group was also significantly reduced. It is important to note that in the evo þ rosi treatment, blood glucose levels were reduced to a degree similar to that of the rosi group, and plasma insulin levels were reduced significantly better than that of rosi group. Furthermore, hepatic lesions associated with fat and glycogen deposition were morphologically improved in the evo and evo þ rosi groups. Conclusion:The results of this study showed that evo exerts an inhibitory effect on in vitro adipocyte differentiation and in vivo obesity, and also an improvement effect on insulin resistance. These desirable effects of evo were noted even in the presence of rosi. These results indicate that evo improves the undesirable effects of rosi, including adipogenesis, body weight gain and hepatotoxicity, while preserving its desirable blood-glucose-lowering effect.

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Evodiamine, a constituent of Evodiae Fructus, induces anti‐proliferating effects in tumor cells

Abstract: he dried, unripe fruit of Evodiae Fructus (Evodia rutaecarpa Benth., Rutaceae) is known as "Goshuyu" in Japanese. In traditional Chinese medicine, it has long been utilized for the treatment of headache, thoracicoabdominal pain, vomiting, cold and reduced blood circulation.

Cited by 124 publications

References 43 publications

Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy

Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy

Evodiamine Abolishes Constitutive and Inducible NF-κB Activation by Inhibiting IκBα Kinase Activation, Thereby Suppressing NF-κB-regulated Antiapoptotic and Metastatic Gene Expression, Up-regulating Apoptosis, and Inhibiting Invasion

Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes

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