[Effect of acetylalkannin from Arnebia euchroma on proliferation, migration, and invasion of human melanoma A375 cells].

This study aimed to explore the effect and mechanism of acetylalkannin from Arnebia euchroma on the proliferation, migration, and invasion of human melanoma A375 cells. A375 cells were divided into a blank group, and low-, medium-, and high-dose acetylalkannin groups(0.5, 1.0, and 2.0 µmol·L~(-1)). The MTT assay was used to detect cell proliferation. Cell scratch and transwell migration assays were used to detect cell migration ability, and the transwell invasion assay was used to detect cell invasion ability. Western blot was used to detect the protein expression of migration and invasion-related N-cadherin, vimentin, matrix metalloproteina-se-9(MMP-9), and Wnt/ß-catenin pathway-related Wnt1, Axin2, glycogen synthase kinase-3ß(GSK-3ß), phosphorylated GSK-3ß(p-GSK-3ß), ß-catenin, cell cycle protein D_1(cyclin D_1), and p21. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) was used to detect the mRNA expression of E-cadherin, matrix metalloproteinase-2(MMP-2), N-cadherin, vimentin, ß-catenin, snail-1, and CD44. MTT results showed that the cell inhibition rates in the acetylalkannin groups significantly increased as compared with that in the blank group(P<0.01). The results of cell scratch and transwell assays showed that compared with the blank group, the acetylalkannin groups showed reduced cell migration and invasion, and migration and invasion rates(P<0.05, P<0.01) and weakened horizontal and vertical migration and invasion abilities. Western blot results showed that compared with the blank group, the high-dose acetylalkannin group showed increased expression of Axin2 protein(P<0.05), and decreased expression of N-cadherin, vimentin, MMP-9, Wnt1, p-GSK-3ß, ß-catenin, cyclin D_1, and p21 proteins(P<0.05, P<0.01). The expression of GSK-3ß protein did not change significantly. PCR results showed that the overall trend of MMP-2, N-cadherin, vimentin, ß-catenin, snail-1, and CD44 mRNA expression was down-regulated(P<0.01), and the expression of E-cadherin mRNA increased(P<0.01). Acetylalkannin can inhibit the proliferation, migration, and invasion of human melanoma A375 cells, and its mechanism of action may be related to the regulation of Wnt/ß-catenin signaling pathway.

Partitioned Extracts of Bauhinia championii Induce G0/G1 Phase Arrest and Apoptosis in Human Colon Cancer Cells.

Bauhinia championii (Benth.) is one of the commonly used herbs in Taiwan. The stem of this plant has been used to treat epigastria pain and rheumatoid arthritis. However, the antitumor activities of this herb have never been reported. This study aims to investigate the mechanism of anticancer activity of the extracts from B. championii (BC). BC was fractionated with a series of organic solvents, including n-hexane (H), ethyl acetate (EA), 1-butanol (B), and water (W). We first investigated the effects of BC-H, BC-EA, BC-B and BC-W partitioned fraction on cell viability. In HCT 116 colon cancer cell lines, BC-EA showed the highest inhibition of cell viability and changed the morphology of cells. With dose- and time-dependent manners, BC-EA inhibited the proliferation of HCT 116 cells by inducing apoptosis and G0/G1 phase arrest of cell cycle. To determine the underlying mechanisms, down-regulated CDK2, Cyclin D, and Cyclin E and up-regulated p16, p21, and p53 may account for the cell cycle arrest, while the apoptotic effect of BC-EA may attribute to increased intracellular Ca2+, loss of mitochondria membrane potential (ΔΨm), increase of Bax, Bak, puma, and AIF, and decrease of Bcl-2. Furthermore, the inactivation of Ras signaling pathway by BC-EA also contributed to its apoptotic effect on HCT 116. Our study demonstrates that BC-EA not only inhibits cell growth but also induces apoptosis through inhibiting Ras signal pathway and increasing p53 expression levels. We suggest that BC-EA may be a new dietary supplement and a useful tool to search for therapeutic candidates against colon cancer.

Ethyl acetate fraction from methanol extraction of Vitis thunbergii var. taiwaniana induced G0 /G1 phase arrest via inhibition of cyclins D and E and induction of apoptosis through caspase-dependent and -independent pathways in human prostate carcinoma DU145 cells.

Vitis thunbergii var. taiwaniana (VTT) is a wild grape native to Taiwan, belonging to the Vitaceae family and Vitis genus, and widely used as folk herbal medicine. It is traditionally used for the treatment of diarrhea, hypertension, neuroprotection, jaundice, and arthritis. We used the wild-collected VTT and sterilized them to establish the plant tissue culture, and then took the leaves for DNA sequencing to determine its original base. We use methanol to extract VTT in four different solvents: 1-butanol, n-hexane, ethyl acetate, and water. These four preliminary extracts were used to treat human prostate cancer DU145 cells in vitro. We use the flow cytometry to check the cell survival situation. Finally, we found the ethyl acetate layer roughing product (referred VTEA) in human prostate cancer apoptotic effects of cell line DU-145. In the present studies, we use the crude extract of VTT to examine whether or not it can induce apoptosis of DU145 cells in vitro. Viability assays for extracts of VTT treatment showed that it had dose-dependent effect on human prostate cancer DU145 cells. We also found that the extract of VTT induces time-dependent mitochondrial and intrinsic-dependent apoptosis pathways. The in vitro cytotoxic effects were investigated by cell cycle analysis and the determination of apoptotic DNA fragmentation in DU145 cells. The cell cycle analysis showed that extracts of VTT induced a significant increase in the number of cells in G0 /G1 phase. The extract of VTT induced chromatin changes and apoptosis of DU145 cells also were confirmed by DAPI and PI staining that were measured by fluorescence microscopy and flow cytometry, respectively. Finally, the expression of relevant proteins was analyzed by Western blot analysis. These results promoted us to further evaluate apoptosis associated proteins and elucidate the possible signal pathway in DU-145 cells after treated with the extract of VTT.

Actein ameliorates hepatobiliary cancer through stemness and p53 signaling regulation.

Actein is isolated from the rthizomes of Cimicifuga foetida, which is a triterpene glycoside, displaying suppressive effects on breast cancer cells proliferation. However, the effects of actein treatment on liver injury, tending to cancer, have little to be known. Thus, the study is conducted to explore the role of actein in early liver cancer. Diethylnitrosamine (DEN) was used to induce liver cancer in mice followed by actein treatment at different concentrations. DEN caused steatohepatitis supported by fibrosis and inflammation, which were ameliorated for actein administration. Liver histology of mice with DEN treatment displayed hepatobiliary cysts, reversed by actein. Cell proliferation markers of Cyclin Ds and p53, as well as cancer stem cell markers of CD133 were highly increased in liver tissue samples from DEN-induced mice, and actein showed inhibitory role in these signals expression. Actein-reduced up-regulation of Hif-1α and VEGFR1 in DEN-stimulated liver tissue of mice was seen. Taken together, DEN promoted liver cancer progression, which was ameliorated by actein, supplying a potential therapeutic strategy for liver cancer in future.

Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.

Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca2+ release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017.

Coptis japonica Makino extract suppresses angiogenesis through regulation of cell cycle-related proteins.

Angiogenesis, neovascularization from pre-existing vessels, is a key step in tumor growth and metastasis, and anti-angiogenic agents that can interfere with these essential steps of cancer development are a promising strategy for human cancer treatment. In this study, we characterized the anti-angiogenic effects of Coptis japonica Makino extract (CJME) and its mechanism of action. CJME significantly inhibited the proliferation, migration, and invasion of vascular endothelial growth factor (VEGF)-stimulated HUVECs. Furthermore, CJME suppressed VEGF-induced tube formation in vitro and VEGF-induced microvessel sprouting ex vivo. According to our study, CJME blocked VEGF-induced cell cycle transition in G1. CJME decreased expression of cell cycle-regulated proteins, including Cyclin D, Cyclin E, Cdk2, and Cdk4 in response to VEGF. Taken together, the results of our study indicate that CJME suppresses VEGF-induced angiogenic events such as proliferation, migration, and tube formation via cell cycle arrest in G1.

The prevention and treatment effects of tanshinone IIA on oestrogen/androgen-induced benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in elderly men. Tanshinone IIA (Tan IIA) is the active ingredient extracted from the traditional Chinese medicine Salvia, and it has effects of anti-oxidation, anti-inflammation, vascular smooth muscle relaxation and tumour growth inhibition. The present study aimed to investigate the therapeutic potential of Tan IIA in the prevention and treatment of BPH. In a rat model of oestradiol/testosterone-induced BPH, Tan IIA inhibited the increase in the thickness of the peri-glandular smooth muscle layer, suppressed the expression of proliferating cell nuclear antigen (PCNA) in both prostate epithelial cells and stromal cells, downregulated the expression of androgen receptor (AR), oestrogen receptor α (ERα), cyclin B1 (CCNB1) and cyclin D1 (CCND1), and effectively prevented the development of the disorder. In vitro, Tan IIA inhibited the proliferation of human prostate stromal cell line WPMY-1 and epithelial cell line RWPE-1 in a dose- and time-dependent manner. In WPMY-1 cells, Tan IIA treatment arrested the cell cycle at the G2/M phase and downregulated the expression of CCNB1. However, in RWPE-1 cells, Tan IIA treatment arrested cell cycle at the G0/G1 phase and reduced the expression of CCND1. Tan IIA also reduced the expression of ERα and AR in WPMY-1 and RWPE-1 cells. These results suggest that Tan IIA can inhibit the growth of prostate stromal and epithelial cells both in vivo and in vitro by a mechanism that may involve arresting the cell cycle and downregulating ERα and AR expression.

Anti-angiogenic effects of Siegesbeckia glabrescens are mediated by suppression of the Akt and p70S6K-dependent signaling pathways.

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we report the effects and molecular mechanism of an ethanolic extract of SG on cell proliferation, migration and tube formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. SG treatment inhibited VEGF-A-stimulated endothelial cell proliferation through downregulation of cyclin D and upregulation of cyclin-dependent kinase inhibitors such as p27Kip1 and p21WAF1/Cip1. In addition, SG inhibited VEGF­A-stimulated endothelial cell migration and tube formation. These anti-angiogenic activities of SG were mediated by inactivation of the Akt- and p70S6K-dependent signaling pathways. Collectively, our findings demonstrate the pharmacological roles and molecular mechanism of SG in regulating angiogenic responses and support further evaluation and development of SG as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Piperine inhibits platelet-derived growth factor-BB-induced proliferation and migration in vascular smooth muscle cells.

The proliferation and migration of vascular smooth muscle cells (VSMCs) in blood vessels are important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Piperine, a major component of black pepper, has antioxidant, anticancer, and anti-inflammatory activity. However, the antiatherosclerotic effects of piperine have not been investigated. In this study, the effects of piperine on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs were investigated. The antiproliferative effects of piperine were determined using MTT assays, cell counting, real-time polymerase chain reaction, and western blots. Our results showed that piperine significantly attenuated the proliferation of VSMCs by increasing the expression of p27(kip1), regulating the mRNA expression of cell cycle enzymes (cyclin D, cyclin E, and PCNA), and decreasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in a noncytotoxic concentration-dependent manner (30-100 µM). Moreover, we examined the effects of piperine on the migration of PDGF-BB-stimulated VSMCs, as determined by the Boyden chamber assay, H2DCFDA staining, and western blots. Our results showed that 100 µM piperine decreased cell migration, the production of reactive oxygen species (ROS), and phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Taken together, our results suggest that piperine inhibits PDGF-BB-induced proliferation and the migration of VSMCs by inducing cell cycle arrest and suppressing MAPK phosphorylation and ROS. These findings suggest that piperine may be beneficial for the treatment of vascular-related disorders and diseases.

Antrodia camphorata induces G(1) cell-cycle arrest in human premyelocytic leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice.

Antrodia camphorata is a well-known medicinal mushroom in Taiwan. The broth from a fermented culture of Antrodia camphorata (AC) has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of AC on cell cycle arrest in vitro in HL-60 cells and on tumor regression in vivo using an athymic nude mouse model. We found that AC (20-80 µg mL(-1)) treatment significantly induced G1 cell-cycle arrest in HL-60 cells by reducing the levels of cyclin D1, CDK4, cyclin E, CDK2, cyclin A, and phosphorylation of retinoblastoma protein (p-Rb). Moreover, AC treatment led to significantly increased protein expression levels of CDK inhibitors, including p21(WAF1) and p15(NIK4B). Additionally, AC treatment markedly induced intracellular ROS generation and mitochondrial dysfunction in HL-60 cells. Furthermore, the in vivo study results revealed that AC treatment was effective in terms of delaying the tumor incidence in nude mice that had been inoculated with HL-60 cells as well as in reducing the tumor burden. Histological analysis confirmed that AC treatment significantly modulated the xenografted tumor progression as demonstrated by a reduction in mitotic cells. Our data strongly suggest that Antrodia camphorata could be an anti-cancer agent for human leukemia.

Maple polyphenols, ginnalins A-C, induce S- and G2/M-cell cycle arrest in colon and breast cancer cells mediated by decreasing cyclins A and D1 levels.

Polyphenols are bioactive compounds found in plant foods. Ginnalins A-C are polyphenols present in the sap and other parts of the sugar and red maple species which are used to produce maple syrup. Here we evaluated the antiproliferative effects of ginnalins A-C on colon (HCT-116) and breast (MCF-7) tumourigenic and non-tumourigenic colon (CCD-18Co) cells and investigated whether these effects were mediated through cell cycle arrest and/or apoptosis. Ginnalins A-C were twofold more effective against the tumourigenic than non-tumourigenic cells. Among the polyphenols, ginnalin A (84%, HCT-116; 49%, MCF-7) was more effective than ginnalins B and C (50%, HCT-116; 30%, MCF-7) at 50 µM concentrations. Ginnalin A did not induce apoptosis of the cancer cells but arrested cell cycle (in the S- and G(2)/M-phases) and decreased cyclins A and D1 protein levels. These results suggest that maple polyphenols may have potential cancer chemopreventive effects mediated through cell cycle arrest.

Pharmacological mechanisms of black cohosh in Sprague-Dawley rats.

BACKGROUND: Studies indicate that extracts and purified components from black cohosh inhibit the growth of human breast cancer cells, but the molecular targets and signaling pathways have not yet been defined. PURPOSE: This study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague-Dawley rats. MATERIALS AND METHODS: To assess effects on gene activity and lipid content, we treated female Sprague-Dawley rats with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 or 0mg/kg. Four animals for each group were sacrificed at 1, 6 and 24h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis. RESULTS: Microarray analysis of rat liver tissue indicated that black cohosh markedly downregulated mitochondrial oxidative phosphorylation genes. Phospholipid biosynthesis and remodeling, PI3-Kinase and sphingosine signaling were upregulated, driven largely by an upregulation of several isoforms of phospholipase C. Hierarchical clustering indicated that black cohosh clustered with antiproliferative compounds, specifically tubulin binding vinca alkaloids and DNA alkylators. In support of this, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited the proliferation of HepG2, p53 positive, liver cancer cells. Black cohosh reduced the level of free fatty acids at 6 and 24h and triglycerides at 6h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24h. CONCLUSION: Our results suggest that black cohosh warrants further study for breast cancer prevention and therapy.

Galbanic acid decreases androgen receptor abundance and signaling and induces G1 arrest in prostate cancer cells.

Androgen receptor (AR) signaling is crucial for the genesis and progression of prostate cancer (PCa). We compared the growth responses of AR(+) LNCaP and LNCaP C4-2 vs. AR(-) DU145 and PC-3 PCa cell lines to galbanic acid (GBA) isolated from the resin of medicinal herb Ferula assafoetida and assessed their connection to AR signaling and cell cycle regulatory pathways. Our results showed that GBA preferentially suppressed AR(+) PCa cell growth than AR(-) PCa cells. GBA induced a caspase-mediated apoptosis that was attenuated by a general caspase inhibitor. Subapoptotic GBA downregulated AR protein in LNCaP cells primarily through promoting its proteasomal degradation, and inhibited AR-dependent transcription without affecting AR nuclear translocation. Whereas docking simulations predicted binding of GBA to the AR ligand binding domain with similarities and differences with the AR antagonist drug bicalutamide (Bic), LNCaP cell culture assays did not detect agonist activity of GBA. GBA and Bic exerted greater than additive inhibitory effect on cell growth when used together. Subapoptotic GBA induced G(1) arrest associated with an inhibition of cyclin/CDK4/6 pathway, especially cyclin D(1) without the causal involvement of cyclin-dependent kinase (CDK) inhibitory proteins P21(Cip1) and P27(Kip1) . In summary, the novelty of GBA as an anti-AR compound resides in the distinction between GBA and Bic with respect to AR protein turnover and a lack of agonist effect. Our observations of anti-AR and cell cycle arrest actions plus the anti-angiogenesis effect reported elsewhere suggest GBA as a multitargeting drug candidate for the prevention and therapy of PCa.

Salviae Miltiorrhizae Radix and Puerariae Lobatae Radix herbal formula mediates anti-atherosclerosis by modulating key atherogenic events both in vascular smooth muscle cells and endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Salviae Miltiorrhizae Radix (Danshen) and Puerariae Lobatae Radix (Gegen) are principal herbs have long been used in combination for treating cardiovascular disease. AIMS OF STUDY: Danshen and Gegen in the ratio of 7:3 (DGW) have significantly reduced the carotid intimal-media thickening (IMT) in patients in our previous clinical study. In the present study, we have demonstrated the mechanisms on IMT reduction by investigating its key processes on both vascular smooth muscle cell (vSMC) and endothelial cells. MATERIALS AND METHODS: The anti-proliferative effects of DGW on platelet-derived growth factor (PDGF) induced vSMC proliferation were studied by cell proliferation, cell cycle distribution, p-ERK and cyclin D expression level. The anti-migratory effect of DGW was investigated by using transwell apparatus. For human umbilical endothelial cells (HUVEC), the inhibitory effects of DGW on TNF-alpha induced cell adhesion, cell adhesion molecules expression, MCP-1 and IL-6 production were investigated. RESULTS: DGW significantly inhibited A7r5 proliferation and exhibited G1/S cell cycle arrest by suppressing both p-ERK and cyclin D expression. Moreover, DGW showed anti-migratory effect against PDGF-induced A7r5 migration. In addition, DGW inhibited the cell adhesion as well as the expression of ICAM-1 and VCAM-1, the production of MCP-1 but not IL-6 in TNF-α stimulated HUVECs. CONCLUSIONS: Our study provided strong scientific evidence on IMT reduction in patients by modulating the key atherogenic events in both vSMC and endothelial cells.

HY253, a novel decahydrofluorene analog, from Aralia continentalis, induces cell cycle arrest at the G1 phase and cytochrome c-mediated apoptosis in human lung cancer A549 cells.

AIM OF THE STUDY: In the course of our screening for novel modulators on cell cycle progression and apoptosis as anticancer drug candidates, we isolated a novel compound HY253 with the molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis. This study was designed to evaluate the detailed mechanisms of cell cycle arrest and the apoptotic induction of HY253 in human lung cancer A549 cells. MATERIALS AND METHODS: To investigate the effects of HY253 on cell cycle progression in A549 cells, we measured DNA content of A549 cells treated with 35 microM of HY253 using flow cytometric analysis. Furthermore, TUNEL assay was used to examine apoptotic induction in A549 cells treated with 70 microM of HY253 for 24 and 48 h. The effects of HY253 on apoptosis-associated and cell cycle regulatory proteins in A549 cells were examined using Western blot analysis. RESULTS: The flow cytometric analysis revealed an appreciable G(1) phase arrest in A549 cells treated with 35 microM of HY253. This HY253-induced G(1) phase arrest is associated with decreased expression of cyclin D and up-regulation of p21(CIP1), via p53 phosphorylation at Ser-15, which resulted in increased hypophosphorylated pRb in A549 cells. Furthermore, TUNEL assay and Western blot analysis revealed an appreciable apoptotic induction in A549 cells treated with 70 microM of HY253 for 48 h. This apoptotic induction in HY253-treated A549 cells is also associated with cytochrome c release from mitochondria which in turn resulted in the activation of caspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). CONCLUSIONS: These results demonstrate that HY253, a novel antiproliferative compound isolated from the roots of Aralia continentalis, induces cell cycle arrest at the G(1) phase and apoptosis in A549 cells. Based on these results, we suggest that HY253 may be a potent cancer chemotherapeutic candidate for use in treating human lung cancer cells via up-regulation and activation of p53 gene.

Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFkappaB, cyclinD and MMP-1 transcription.

Curcumin, an active constituent of turmeric, has been shown to possess inhibitory effect of cell proliferation and induction of apoptosis towards a board range of tumors. Cell inhibition activities of curcumin are behaved differently in various cell types. To investigate the mechanism basis for the cell inhibition of curcumin on breast cancer cell lines, we examine curcumin effect on NFkappaB, cell cycle regulatory proteins and matrix metalloproteinases (MMPs) in two breast cancer cell lines (MDA-MB-231 and BT-483). Cell proliferation was performed by water soluble tetrazolium WST-1 assay. The effect of curcumin's on the activity of matrix metalloproteinase-1, 3, 9 were analyzed by RT-PCR. Cell cycle regulatory protein including cyclin D1, CDK4 and p21 were examined by immunochemistry. The expressions of NFkappaB in breast cancer cells treated with curcumin were studied by immunochemistry and western blot. The results from WST-1 cell proliferation assay showed that curcumin exhibited the anti-proliferation effect on MDA-MB-231 and BT-483 cells in a time- and dose-dependent manner. In response to the treatment, while, the expression of cyclin D1 had declined in MDA-MB-231 and the expression of CDK4 in BT-483 had declined. MMP1 mRNA expression in BT-483 and MDA-MB-231 had significantly decreased in curcumin treatment group compared with control group. Our finding extrapolates the antitumor activity of curcumin in mediating the breast cancer cell proliferative rate and invasion by down-regulating the NFkappaB inducing genes.