Inhibitory effects of evodiamine on the growth of human prostate cancer cell line LNCaP

Abstract

Key words: prostate cancer; evodiamine; cell growth; G2/M arrest; apoptosisProstate cancer is the most commonly diagnosed malignancy in American men over 40 years of age and is the second leading of cancer deaths. 1,2 Recently, prostate cancer has become more and more common in Asia including Taiwan. 3 According to previous studies, widely accepted risk factors for prostate cancer are age, race, ethnicity, dietary habits, androgen production and metabolism. 4 Prostate cancer is characterized by an initial androgen dependency in which the growth of cancer is enhanced by androgen. 5 In this stage, treatment is aimed at either lowering the plasma level of testosterone or inhibiting its biological effects or those of its metabolites at the target tissue levels. Orchidectomy, LHRH agonists and antiandrogenic drugs have been used clinically for treatment of androgen-dependent prostate cancer. 6 -8 However, these therapies cause psychological and physiological side effects. 9 -11 The drugs for androgen-dependent prostate cancer have merits and limitations. Because of the side effects and limitations of the currently available treatments, there is a need to identify and develop new antitumor agents against androgen-dependent prostate cancer.It has been demonstrated that several microchemicals that are isolated from herbs and plants with diversified pharmacological properties exert inhibitory effects on the proliferation of cancer. [12][13][14][15][16] The microchemicals could be the most desirable agents for prevention or intervention of human cancer incidence and mortality due to stomach, colon, breast, esophagus, lung, bladder and even prostate carcinoma. [17][18][19] Our previous studies showed that cardiac glycosides from digitalis and Chansu exhibited the antiproliferative effects on prostate cancer cells including DU145, PC3 and LNCaP to mediate the elevated [Ca2 ϩ ] i and apoptosis. 19,20 Wu-Chu-Yu is a long-standing Chinese herb used for syndromes characterized by cold hands and gastrointestinal disorders. Evodiamine is one of the major bioactive compounds isolated and purified from Wu-Chu-Yu. It has been demonstrated that evodiamine influences many physiological functions including vasotension, anoxia and body temperature. [21][22][23] Meanwhile, evodiamine exhibits an anti-inflammatory effect on change of nitric oxide production in murine macrophage. 24 Recently, we found that evodiamine inhibited testosterone production via a decrease of 17␤-hydroxysteroid dehydrogenase activity in testicular interstitial cells. 25 Interestingly, the evidence showed that rutaecarpine, the other bioactive compound isolated from Wu-Chu-Yu, inhibited the growth of many kinds of cancers including breast, lung and kidney cancers. 26 Furthermore, Okasawara et al. 27,28 reported that evodiamine inhibited the cell proliferation, cell migration and lung metastasis of murine colon cancer cells.According to previous reports, evodiamine has been recognized as a compound for anti-metastatic and anti-tumor agent in colon cancer cells. It w...

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

“…That evodiamine down-regulates Cyclin D1 expression may explain the results from earlier reports indicating that this agent induces G 2 /M arrest rather than G 1 /S arrest (4,5). It also may explain the antiproliferative effects of evodiamine through TNF-induced NF-B-mediated down-regulation of Cyclin D1 by evodiamine.…”

“…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.…”

Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling

“…Currently, evidence indicates that EVO possesses anticancer activities. EVO is reported to hinder tumor development by inhibiting cancer cell proliferation and inducing cell apoptosis in various types of cancer cells, such as lung (14), acute leukemia (15)(16)(17), prostate (18)(19)(20) and cervical (17). Yang et al reported that EVO can upregulate the expression of phosphatase shatterproof 1 (SHP-1) (21), which is the key gene of IL-6-induced signal transducer and activator of transcription signaling 3 (STAT3) signaling leading to the suppression of survival and proliferation in hepatocellular carcinoma cells.…”

Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells

“…Natural products have provided a large number of currently used chemotherapeutics and will continue to be an important component of drug discovery (24,25). Evodiamine, an alkaloidal component extracted from the fruit of Evodiae fructus, has been reported to inhibit various tumor cell proliferations, including monocytic leukemia (26), melanoma (27), prostate cancer (28), and breast cancer cell (29). However, the mechanism underlying its antiproliferative, antimetastatic, and apoptotic activities is poorly defined yet.…”