Synthesis and biological evaluation of new cyclic amidine analogs of chlorambucil

A number of novel cyclic amidine analogs of chlorambucil were synthesized and examined for cytotoxicity in breast cancer cell cultures and for inhibition of topoisomerases I and II. Evaluation of the cytotoxicity of these compounds employing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and inhibition of [(3)H]-thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than chlorambucil. The degree to which these compounds inhibited cell growth breast cancer cells was directly correlated to DNA-binding affinity. These studies indicate that cyclic amidine analogs of chlorambucil are a potent catalytic inhibitor of topoisomerase II but not topoisomerase I. The highest degree of DNA binding and cytotoxicity in both MDA-MB-231 and MCF-7 breast cancer cells was observed for the compound, which possess a 4,5-dihydro-1H-imidazol moiety.     

Novel amidine analogue of melphalan as a specific multifunctional inhibitor of growth and metabolism of human breast cancer cells

A novel amidine analogue of melphalan (AB4) was compared to its parent drug, melphalan in respect to cytotoxicity, DNA and collagen biosynthesis in MDA-MB-231 and MCF-7 human breast cancer cells. It was found that AB4 was more active inhibitor of DNA and collagen synthesis as well more cytotoxic agent than melphalan. The topoisomerase I/II inhibition assay indicated that AB4 is a potent catalytic inhibitor of topoisomerase II. Data from the ethidium displacement assay showed that AB4 intercalated into the minor-groove at AT sequences of DNA. The greater potency of AB4 to suppress collagen synthesis was found to be accompanied by a stronger inhibition of prolidase activity and expression compared to melphalan. The phenomenon was related to the inhibition of beta(1)-integrin and IGF-I receptor mediated signaling caused by AB4. The expression of beta(1)-integrin receptor, as well as Sos-1 and phosphorylated MAPK, ERK(1) and ERK(2) but not FAK, Shc, and Grb-2 was significantly decreased in cells incubated for 24h with 20 microM AB4 compared to the control, not treated cells, whereas in the same conditions melphalan did not evoke any changes in expression of all these signaling proteins, as shown by Western immunoblot analysis. These results indicate the amidine analogue of melphalan, AB4 represent multifunctional inhibitor of breast cancer cells growth and metabolism.     

Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancer cells

High concentrations of specific catechins [epigallocatechin gallate (EGCG), epigallocatechin (EGC) and epicatechin gallate (ECG)] inhibit the proliferation of many different cancer cell lines. The aim of this work was to determine if low concentrations of catechins with and without 4-hydroxytamoxifen (4-OHT) co-treatment would cause significant cytotoxicity in estrogen receptor-positive (ERalpha+) and -negative (ERalpha-) human breast cancer cells. Therefore, MCF-7, T47D, MDA-MB-231 and HS578T cells were incubated with EGCG, EGC or ECG (5-25 microM) individually and in combination with 4-OHT for 7 days. Cell number was determined by the sulforhodamine B cell proliferation assay. As single agents, none of the catechins were cytotoxic to T47D cells, while only EGCG (20 microM) elicited cytotoxicity in MCF-7 cells. Additionally, no benefit was gained by combination treatment with 4-OHT. ERalpha- human breast cancer cells were more susceptible as all three catechins were significantly cytotoxic to HS578T cells at concentrations of 10 microM. In this cell line, combination with 4-OHT did not increase cytotoxicity. However, the most striking results were produced in MDA-MB-231 cells. In this cell line, EGCG (25 microM) produced a greater cytotoxic effect than 4-OHT (1 microM) and the combination of the two resulted in synergistic cytotoxicity. In conclusion, low concentrations of catechins are cytotoxic to ERalpha- human breast cancer cells, and the combination of EGCG and 4-OHT elicits synergistic cytotoxicity in MDA-MB-231 cells.     

Effect of Guizhi Fuling capsule and its extracts on human breast cancer cells proliferation

OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL~(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.     

Cytotoxic activity of G3 PAMAM-NH₂ dendrimer-chlorambucil conjugate in human breast cancer cells

Evaluation of the cytotoxicity of a novel G3 PAMAM-NH(2) dendrimer-chlorambucil conjugate employing a MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that the conjugate was more potent antiproliferative agent than chlorambucil. It was found that dendrimer-chlorambucil conjugate was more active inhibitor of collagen biosynthesis than chlorambucil. Our experiments carried out with flow cytometry assessment of annexin V binding and fluorescent microscopy assay revealed that PAMAM-CH conjugate inhibited the proliferation of MCF-7 and MDA-231 malignant cells by increasing the number of apoptotic and necrotic cells. The apoptotic effect of PAMAM-CH conjugate was found to be stronger than that caused by chlorambucil.     

Licofelone-nitric oxide donors as anticancer agents

Five licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) nitric oxide donor conjugates were developed by a parallel synthesis approach. The biological screening revealed that compounds with a propyl (6b), butyl (6c), or octyl (6d) chain between licofelone and the nitric oxide donor exhibited high antiproliferative potency at MCF-7 and MDA-MB-231 breast cancer as well as at HT-29 colon cancer cells. Moreover, 6b-d possessed at least 2-fold higher cytotoxicity at MDA-MB-231 cells than the parent compound licofelone although they showed less inhibitory activity at COX-1 and COX-2. A correlation between COX inhibition and growth inhibitory properties is not visible. However, the high levels of nitric oxide production of the compounds may result in their high cytotoxic activity.     

Cytotoxicity and induction of apoptosis of human breast cancer cells by novel platinum(II) complexes

The current work investigates the influence of novel dinuclear platinum(II) compounds of structure: Pt₂(3-ethylpyridine)₄(berenil)₂ (Pt10) and Pt₂(3-butylpyridine)₄(berenil)₂ (Pt11) on growth and viability of MDA-MB-231 and MCF-7 breast cancer cells as well as their putative mechanism of cytotoxicity. Evaluation of the cytotoxicity of Pt10 and Pt11 employing a MTT assay and inhibition of [³H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more potent antiproliferative agents than cisplatin. In our study the induction of apoptosis by Pt10 and Pt11 in human breast cancer cells was confirmed by several biochemical markers, such as: phosphatidylserine externalization, loss of mitochondrial membrane potential ΔΨ_m, caspase-3, -8, -9 activity, and DNA degradation. Pt10 and Pt11 induce apoptosis of breast cancer cells via mechanisms dependent on caspases activation and associated with mitochondrial membrane potential disruption.     

Synthesis, DNA-binding affinity and cytotoxicity of the dinuclear platinum(II) complexes with berenil and amines ligands

A series of platinium(II) complexes of formula [Pt2L4(berenil)2]Cl4.4HCl.2H2O where L is piperidine (1), 4-picoline (2), 3-picoline (3) or isopropylamine (4) was prepared and their cytotoxicity have been tested against the growth of human breast cancer cells. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than cisplatin. Data from the ethidium displacement assay indicated that these compounds show moderate specificity for AT base pairs of DNA. Compounds 1-4 were also potent topoisomerase II inhibitors, with 50% inhibitory concentrations (IC50) ranging from 5 to 50 microM.     

Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of the ERα-mediated signaling pathway

Aim:

To investigate the anticancer mechanisms of triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook F, against human breast cancer cells and the involvement of the estrogen receptor-α (ERα)-mediated signaling pathway in particular.

Methods:

Human breast cancer ERα-positive MCF-7 cells and ERα-negative MDA-MB-231 cells were tested. PrestoBlue assay was used to evaluate the cell viability. The levels of ERα mRNA and protein were detected with real-time PCR and immunoblotting, respectively. Mouse models of MCF-7 or MDA-MB-231 xenograft tumors were treated with triptolide (0.4 mg·kg⁻¹·d⁻¹, po) or a selective estrogen receptor modulator tamoxifen (mg·kg⁻¹·d⁻¹, po) for 3 weeks, and the tumor weight and volume were measured.

Results:

Triptolide (5–200 nmol/L) dose-dependently inhibited the viability of both MCF-7 and MDA-MB-231 cells, with a more potent inhibition on MCF-7 cells. Knockdown of ERα in MCF-7 cells by siRNA significantly attenuated the cytotoxicity of triptolide, whereas overexpression of ERα in MDA-MB-231 cells markedly enhanced the cytotoxicity. Triptolide dose-dependently decreased the expression of ERα in MCF-7 cells and MCF-7 xenograft tumors. Furthermore, treatment of MCF-7 cells with triptolide inhibited the phosphorylation of ERK1/2 in dose- and time-dependent manners. In the mice xenografted with MCF-7 cells, treatment with triptolide or tamoxifen resulted in significant reduction in the tumor weight and volume. Similar effects were not obtained in the mice xenografted with MDA-MB-231 cells.

Conclusion:

The anticancer activity of triptolide against ERα-positive human breast cancer is partially mediated by downregulation of the ERα-mediated signaling pathway.     

Cytotoxicity,cell cycle arrest,and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan)

An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5 μg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24 h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 h for MCF-7 cells and 24 h for MDA-MB-231cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines.     

Different apoptotic effects of saxifragifolin C in human breast cancer cells

Breast cancer is currently the most common form of cancer affecting women. Recent studies have reported that triterpenoid saponins isolated from Androsace umbellata exhibit anti-proliferative effects in several types of cancer cells. However, the cytotoxic effect of saxifragifolin C (Saxi C) on breast cancer cells remains unclear. The purpose of this study is to evaluate the in vitro anti-tumor activity of Saxi C in human breast cancer cells. Our data indicated that MDA-MB-231 cells were more sensitive than MCF-7 cells to Saxi C treatment. In addition, Saxi C inhibited cell survival through the induction of reactive oxygen species and the caspase-dependent pathway in the MDA-MB-231 cells, whereas MCF-7 cells treated with Saxi C underwent the apoptotic cell death in a caspase-independent manner. Although Saxi C treatment resulted in the induction of activation of MAPKs in both types of human breast cancer cells, p38 MAPK and JNK, but not ERK1/2, appeared to be involved in Saxi C-induced apoptosis. Moreover, ERα-overexpressing MDA-MB-231 cells remained alive, whereas the survival of shERα-transfected MCF-7 cells decreased. Taken together, Saxi C induced apoptosis in MCF-7 cells and MDA-MB-231 cells via different regulatory mechanisms, and ERα status might be essential for regulating Saxi C-induced apoptosis in breast cancer cells. Thus, Saxi C is a potential chemotherapeutic agent in breast cancer.     

Growth factors and chemotherapeutic modulation of breast cancer cells

A variety of molecules including growth factors are involved in the metastasis of breast cancer cells to bone. We have investigated the effects of osteoblast derived growth factors, such as insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-beta1), on doxorubicin (adriamycin)-induced apoptosis and growth arrest of estrogen receptor positive (ER+) (MCF-7) and negative (ER-) (MDA-MB-435) breast cancer cell lines. Human breast normal epithelial (MCF-10A), breast cancer (MCF-7) and metastatic breast cancer (MDA-MB-435) cell lines were exposed to different doses of doxorubicin (0.1, 1 or 10 microM) at various exposure times (12, 24 or 48 h). The doxorubicin cytotoxicity was found to be higher in cancer cell lines (MDA-MB-435 and MCF-7) compared with normal breast epithelial cells (MCF-10A cells). Doxorubicin appeared to exert a blockade of MCF-7 and MDA-MB-435 cells at the G2/M phase, and induced apoptosis in MDA-MB-435 (29 +/- 4.2% vs 3.4 +/- 1.9% control) as assessed by flow cytometry, DNA fragmentation and terminal deoxynucleotidyl-transferase mediated deoxyuridine 5-triphosphate and biotin nick-end labelling (TUNEL) assays. Estradiol (E2) stimulated the growth of MCF-7 cells and increased the distribution of the cells at the G2/M and S phases. Exogenous IGF-1 partially neutralized the doxorubicin cytotoxicity in both cancer cell lines (MCF-7 and MDA-MB-435). Similarly, TGF-beta1 partially neutralized the doxorubicin cytotoxicity in MDA-MB-435 cells by reducing the number of cells at the 相似文献   

高强度聚焦超声通过TRIF介导的ERK通路增强乳腺癌的顺铂化疗敏感性

目的　探究高强度聚焦超声（HIFU）通过β干扰素TIR结构域衔接蛋白（TRIF）介导的细胞外调节蛋白激酶（ERK）通路增强乳腺癌顺铂（DDP）化疗敏感性的作用机制。方法　依次增加DDP浓度间歇作用的方法诱导乳腺癌细胞（MDA-MB-231、MCF-7）/DDP耐药细胞;将MDA-MB-231/DDP、MCF-7/DDP细胞分为control组、HIFU组、HIFU+二甲基亚砜（DMSO）组、HIFU+漆黄素（fisetin）组。CCK-8检测细胞活力;集落形成实验检测细胞增殖情况;流式细胞术检测细胞周期及凋亡情况;Western blot检测细胞TRIF蛋白、耐药相关蛋白及ERK通路蛋白表达;体内成瘤实验检测肿瘤生长情况;免疫组化染色法检测肿瘤组织Ki-67的表达。结果　与亲本MDA-MB-231及MCF-7细胞相比,在相同浓度DDP处理下MDA-MB-231/DDP及MCF-7/DDP细胞活力更高,且半数抑制浓度（IC50）显著增加（P＜0.05）,成功建立了稳定的DPP耐药细胞系;与control组相比,HIFU组MDA-MB-231/DDP及MCF-7/DDP细胞IC50、OD450值、克隆细胞数、S期细胞百分比、B淋巴细胞瘤-2基因（Bcl-2）、TRIF、p-糖蛋白（p-gp）、多药耐药基因1（MDR1）、p-ERK1/2/ERK1/2表达水平显著降低,G0/G1期细胞百分比、细胞凋亡率、Bcl-2关联X蛋白（Bax）表达水平显著增加（P＜0.05）;与HIFU组相比,HIFU+fisetin组细胞IC50、OD450值、克隆细胞数、S期细胞百分比、Bcl-2、TRIF、p-gp、MDR1、p-ERK1/2/ERK1/2表达水平显著增加,G0/G1期细胞百分比、细胞凋亡率、Bax表达水平显著降低（P＜0.05）。与control组相比,HIFU组肿瘤体积、肿瘤质量、TRIF及p-ERK1/2/ERK1/2表达水平、Ki-67阳性表达显著降低（P＜0.05）;与HIFU组相比,HIFU+fisetin组肿瘤体积、肿瘤质量、TRIF及p-ERK1/2/ERK1/2表达水平、Ki-67阳性表达显著增加（P＜0.05）。结论　HIFU通过抑制TRIF表达来抑制其介导的ERK通路,从而增强乳腺癌DDP化疗敏感性。     

Cytotoxic and genotoxic potentials of newly synthesized antiviral aminopyrazoloquinoline derivatives

In the present study, we screened newly synthesized antiviral aminopyrazoloquinoline derivatives for their cytotoxic and genotoxic potential in human normal and breast cancer cell lines using apoptosis and DNA adducts biomarkers. The compounds, along with the well-known antiviral drug acyclovir, were incubated with the normal (MCF-10A, MCF-12A) and cancer (MCF-7, MDA-MB-231) cell lines at 10, 50, and 100 μM for 72 h at 37°C. The most potent antiviral methoxy derivative (compound 3) was found to be more cytotoxic in the normal breast epithelial cell lines (MCF-10A and MCF-12A) and MDA-MB-231 cell lines at 50 μM. MCF-7 cells were found to be almost completely resistant to all these compounds while MDA-MB-231 cell lines were significantly killed by apoptosis. Acyclovir was ineffective in all these cell lines. We further tested these compounds using modulation of benzo[a]pyrene (BP)-DNA adduct formation in these cell lines. An inverse correlation was found between the degree of apoptosis and BP-DNA adduct levels for most of these compounds, although this seems to be the case only with the cancer cell lines. Our results suggest that the newly synthesized antiviral compounds have an associated risk of cytotoxicity and/or genotoxicity compared to acyclovir.     

Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents

The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the β-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46 and 47 displayed the most potent antiproliferative activity of the series. β-Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells (IC??= 0.8 nM) together with significant in vitro inhibition of tubulin polymerization and has been selected for further biochemical assessment. These novel β-lactam compounds are identified as potentially useful scaffolds for the further development of antitumor agents that target tubulin.     

Coenzyme Q0 induces apoptosis and modulates the cell cycle in estrogen receptor negative breast cancer cells

We postulated that methoxy-substituted cyclic compounds could inhibit estrogen receptor (ER) negative breast cancer growth in vitro. Therefore, this study assessed the cytotoxic potential of various methoxy-substituted cyclic compounds [7,8-dimethoxyflavone, 4-methoxyphenylacetic acid, 2-methoxyphenylacetic acid, 4-methoxybenzophenone, 5-methoxy-1-indanone, and coenzyme Q0 (CoQ0)] toward ER-negative human breast cancer cells (MDA-MB-231 and SKBr3). Cytotoxicity was assessed using the sulforhodamine B assay. CoQ0 demonstrated the strongest cytotoxicity toward MDA-MB-231 and SKBr3 cells with IC50 values of 1.7 micromol/l and 3.1 micromol/l, respectively, whereas the other compounds were either much less potent or completely lacked cytotoxicity toward both breast cancer cell lines. Therefore, only CoQ0 was examined for its ability to modulate cell cycle progression and induce apoptosis. Cell cycle experiments, using propidium iodide staining and flow cytometry, demonstrated that CoQ0 at 7.5 micromol/l increased the proportion of MDA-MB-231 cells in G1/G0-phase by 16.6+/-0.6% of control (P<0.05), and increased in the proportion of S-phase SKBr3 cells by 37.8+/-5.8% over control (P<0.05). Induction of apoptosis was determined using propidium iodide/Annexin-V-FLUOS staining followed by flow cytometry. The results demonstrated that treatment with CoQ0 (7.5 micromol/l) increased the proportion of apoptotic MDA-MB-231 and SKBr3 cells by 12-fold and 4-fold over control (P<0.05), respectively. Thus, CoQ0 is a potent cytotoxic drug that induces apoptosis and modulates cell cycle progression in ER-negative breast cancer cells. Therefore, CoQ0 is an appropriate candidate for further study and development as a potential drug for ER-negative breast cancer.     

RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro via intracellular ROS accumulation

Aim： Receptor-interacting protein 3 （RIP3） is involved in tumor necrosis factor receptor signaling, and results in NF-KB-mediated prosurvival signaling and programmed cell death. The aim of this study was to determine whether overexpression of the RIP3 gene could sensitize human breast cancer cells to parthenolide in vitro. Methods： The expression of RIP3 mRNA in human breast cancer cell lines （MCF-7, MDA-MB-231, MDA-MB-435 and T47D） was detected using RT-PCR. Both MDA-MB-231 and MCF-7 cells were transfected with RIP3 expression or blank vectors via lentivirus. Cell viability was measured with MTT assay; intracellular ROS level and cell apoptosis were analyzed using flow cytometry. Results： RIP3 mRNA expression was not detected in the four human breast cancer cell lines tested. However, the transfection induced higher levels of RIP3 protein in MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of RIP3 decreased the IC50 values of parthenolide from 17.6 to 12.6 μmol/L in MCF-7 cells, and from 16.6 to 9.9 μmol/L in MDA-MB-231 cells. Moreover, overexpression of RIP3 significantly increased parthenolide-induced apoptosis and ROS accumulation in MCF-7 and MDA-MB-231 cells. Pretreatment with N-acetyl-cysteine abrogated the increased sensitivity of RIP3-transfected MCF-7 and MDA-MB-231 cells to parthenolide. Conclusion： Overexpression of RIP3 sensitizes MCF-7 and MDA-MB-231 breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.     

Berberine inhibits growth of the breast cancer cell lines MCF-7 and MDA-MB-231

The effects of berberine on the behavior of breast tumors have not yet been established. To determine whether this compound is useful in the treatment of breast cancer, we analyzed the impact of berberine on the human breast cancer cell lines MCF-7 and MDA-MB-231 cells. Berberine was added to proliferating MCF-7 and MDA-MB-231 cells in culture. Following treatment, changes in cell growth characteristics such as proliferation, cell cycle duration, and the degree of apoptosis were assayed. Following berberine treatment, a time-dependent reduction in proliferation was observed in both cell lines at differing concentrations: 20 microM for MCF-7 and 10 microM for MDA-MB-231 cells. Annexin V staining showed an increase in apoptosis in both cell lines of 31 % in MCF-7 and 12 % in MDA-MB-231 cells compared to their respective controls. In addition, 12 % of the MCF-7 cells were arrested at G0/G1, compared to 62 % of control cells. These results demonstrate that treatment with berberine inhibits growth in both MDA-MB-231 and MCF-7 cells. In addition, they show that this partly occurs through the induction of apoptosis in MDA-MB-231 cells, and through both cell cycle arrest and induction of apoptosis in MCF-7 cells. Thus, berberine may be a novel therapeutic drug for breast cancer.