Breast Adenocarcinoma Cell Line MCF-7 Research Articles

Influence of gold nanoparticle architecture on in vitro bioimaging and cellular uptake

Gold nanoparticles (GNPs) are favorable nanostructures for several biological applications due to their easy synthesis and biocompatible properties. Commonly studied GNP shapes are nanosphere (AuNS), nanorod (AuNR), and nanocage (AuNC). In addition to distinct geometries and structural symmetries, these shapes have different photophysical properties detected by surface plasmon resonances. Therefore, choosing the best shaped GNP for a specific purpose is crucial to the success of the application. In this study, all three shapes of GNP were investigated for their potency to interact with cell surface receptors. Anti-HER2 antibody was conjugated to the surface of nanoparticles. MCF-7 breast adenocarcinoma and hMSC human mesenchymal cell lines were treated with GNPs and analyzed for cellular uptake and bioimaging efficiencies using the UV–vis spectroscopy and dark-field microscopy.

Impact of carbon nanomaterials on the formation of multicellular spheroids by tumor cells

This paper investigates the effect of different concentrations of nanostructured materials: fullerene-like (C60), onion-like carbon (OLC) and ultradispersed diamonds (UDD) on the formation of multicellular spheroids. The chemical composition and purity of nanomaterials are controlled by Fourier transform infrared spectroscopy. The strength and direction of the impact of nanomaterials on the cell population was assessed using microphotography of tumor multicellular spheroids of breast adenocarcinoma cell line MCF-7 in vitro and Pearson's correlation coefficient. The results demonstrated that UDD and OLC reduced adhesion and cohesive ability of cells and stimulated generation of cell spheroids of ∼3 × 10−3 mm3 in significant amount. The fullerenes reduced in the main cell adhesion to substrate that led to formation of cell aggregates of ∼5 × 10−3 mm3. The results could be useful for achievement of the directed cell growth in three-dimensional culture.

Evaluation of antioxidant, in vitro cytotoxicity of micropropagated and naturally grown plants of Leptadenia reticulata (Retz.) Wight & Arn.-an endangered medicinal plant

ObjectiveTo evaluate the antioxidant and anti proliferative potential of different solvent extract of micropropagated and naturally grown plants of Leptadenia reticulata against various cancer cell lines. MethodsIn this study different extract were tested for cytotoxicity against human breast adenocarcinoma cell line MCF-7, human colon adenocarcinoma grade II cell line HT-29 and non cancer skeletal muscle cell line L6 through 3-(4, 5–dimethyl thiazol–2–yl)–5–diphenyl tetrazolium bromide assay. The total antioxidant potential was estimated by three different antioxidant model diphenylpicrylhydrazyl free radical scavenging activity, H2O2 scavenging activity and FeCl3 reducing activity. ResultsThe ethyl acetate extract of both naturally grown plant and tissue cultured plant exhibited significant cytotoxicity with IC50 values of 21 µg/mL, 26 µg/mL and 22 µg/mL; 20 µg/mL, 30 µg/mL and 18 µg/mL respectively against three cell lines. The diphenylpicrylhydrazyl free radical scavenging activity was found to be highest with IC50 value of 267.13 µg/mL in ethyl acetate extract. The methanolic extract exhibited moderate antioxidant activity with IC50 value of 510.15 µg/mL. A highly positive correlation was observed between the antioxidant potential and cytotoxic activity of the plant. ConclusionsThe strong cytotoxicity of ethyl acetate extract revealed anti carcinogenic potential of the plant which supports its traditional use as medicine. The present investigation is new to literature till date and will provide better scientific basis for future pharmacological, in vivo studies and novel source of pure bioactive compounds having anti cancer properties in this plant.

Inhibition of telomerase activity by dominant-negative hTERT retards the growth of breast cancer cells.

Telomerase, a ribonucleoprotein enzyme mainly consisted of a catalytic protein subunit human telomerase reverse transcriptase (hTERT) and a human telomerase RNA component, is responsible for maintaining telomeres. Telomerase over-expression correlates significantly with tumors and is a prognostic marker. However, telomerase over-expression in breast cancers and the effect of telomerase inhibition as a candidate cancer therapy are unknown. We used the dominant-negative mutant of hTERT (DN-hTERT) to inhibit telomerase activity on human breast adenocarcinoma cell line MCF-7 by transfection. Telomeric repeat amplification protocol assays and real-time quantitative RT-PCR were performed to investigate telomerase activity as well as expression of hTERT. Telomere length was measured by the flow-fluorescence in situ hybridization assay. Cell proliferation was assessed by the WST-8 assay, and apoptosis was evaluated by flow cytometry. The tumor formation ability of MCF-7 cells was investigated by transplanting cells subcutaneously into BALB/c nude mice. Ectopic expression of DN-hTERT caused dramatically inhibition of telomerase activity and reduction of telomere length. Telomerase inhibition induced growth arrest and apoptosis of MCF7 cells in vitro and loss of tumorigenic properties in vivo. This study shows that telomerase inhibition by DN-hTERT can effectively inhibit the cell viability and tumorigenicity of MCF7 cells and is an attractive approach for breast cancer therapy.

Synthesis, Characterization, and Antiproliferative Activity of Cu2+, V(IV)O2+, Co2+, Mn2+, and Ni2+ Complexes with 3-(2-(4-Methoxyphenylcarbamothioyl)Hydrazinyl)-3-OXO-N-(Thiazol-2-yl)Propanamide against Human Breast Adenocarcinoma Cells

3-(2-(4-methoxyphenylcarbamothioyl)hydrazinyl)-3-oxo-N-(thiazol-2-yl)propan-amide (H4L) has been synthesized and its structure has been confirmed by elemental analysis, IR, mass, and 1H and 13C NMR spectroscopy. This ligand has been used to synthesize complexes with Cu2+, V(IV)O2+, Co2+, Mn2+, and Ni2+. The structures of these complexes have been verified by elemental analyses, molar conductivities, magnetic measurements as well as UV–VIS, IR, 1H-NMR spectroscopy. The IR spectra showed that H4L acts as a uni-negative tetradentate or bidentate ligand. The molar conductance measurements proved that all complexes are nonelectrolytes except complexes 2 and 3. Moreover, the metal complexes geometrical arrangements were square planar, tetrahedral, square-pyramidal, or octahedral. The structures are consistent with the IR, UV–VIS, ESR, as well as conductivity measurements. The antiproliferative activity of the synthesized complexes against human breast adenocarcinoma MCF-7 cell line showed exploited potent to moderate growth inhibitory activity, in particular complex 4 which exhibited superior potency to the reference drug cisplatin. The antitumor activity of these compounds was accompanied by significant increase in the activity of superoxide dismutase with concomitant decrease in the activities of catalase and glutathione peroxidase and reduced glutathione level. The overproduction of free radicals allowed reactive oxygen species-mediated tumor cells death.

Chemical composition, antibacterial activity, and cytotoxicity of essential oil from Nepeta ucrainica L. spp. kopetdaghensis

Chemical composition, antibacterial activity, and cytotoxicity of essential oil (EO) obtained from the aerial parts of Nepeta ucrainica L. spp. kopetdaghensis was investigated in the present study. Chemical composition of the EO was analyzed using GC–MS method. Sixty compounds representing 98.7% of the total oil were characterized. The oil was predominated by sesquiterpene hydrocarbons, and the main components were germacrene D (53.0%), bicyclogermacrene (6.4%), β-bourbonene (4.3%), β-elemene (3.3%), spathulenol (3.2%), cubenol (2.8%), trans-caryophyllene (2.8%), germacrene A (2.1%), and δ-cadinene (2.0%). The antibacterial activity of the EO was investigated against 6 bacterial strains using serial dilution method. The essential oil showed a good activity against Gram-positive bacteria particularly Staphylococcus aureus (minimum inhibitory concentration [MIC]=14μg/mL, minimum bactericidal concentration [MBC]=14μg/mL), but Gram-negative bacteria were resistant to the oil. Also, the cytotoxic effects of the EO on human ovarian carcinoma A2780 cell line and human breast adenocarcinoma MCF-7 cell line were examined using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide [MTT] assay. The EO was found to be cytotoxic against the tested cell lines, with IC50 values less than 50μg/mL for both A2780 and MCF-7 cells.

Efficient Synthesis and Antitumor Activities of Indioside E Analogs

An efficient synthesis of seven analogs of a naturally occurring saponin, indioside E, is described. The synthesis used a 3,4,6-O-protected D-galactopyranosyl thioglycoside as the key intermediate to enable regioselective glycosylation and one-pot multistep reactions. Antitumor activities of the synthetic saponins against a human hepatocellular carcinoma cell line BEL-7402 and a human breast adenocarcinoma cell line MCF-7 were evaluated by means of the CCK-8 assay. Analogs carrying trisaccharides with the D-xylopyranose in indioside E substituted with a D-ribopyranose and an L-arabinopyranose or with its diosgenin aglycon replaced with tigogenin exhibited similar antitumor activities as indioside E, but not other analogs.

Low-density microarray analysis of TGFβ1-dependent cell cycle regulation in human breast adenocarcinoma MCF7 cell line

Low-density microarray analysis of TGFβ1-dependent cell cycle regulation in human breast adenocarcinoma MCF7 cell line

The LIM domain protein FHL1C interacts with tight junction protein ZO-1 contributing to the epithelial–mesenchymal transition (EMT) of a breast adenocarcinoma cell line

FHL1C is a LIM domain protein that has been implied in transcription regulation through interacting with other proteins, such as RBP-J, the critical transcription factor of the Notch signaling pathway. The LIM domain is a protein-protein interaction interface, suggesting that FHL1C could bind other proteins to enable its functions. In order to explore the interacting proteins with FHL1C, in this study we screened FHL1C-interacting proteins by using immunoprecipitation and mass spectrometric analysis. ZO-1, a member of the Zonula occludens proteins that constitute tight junctions, was sorted out as one candidate by using these techniques. Furthermore, we confirmed the interaction between FHL1C and ZO-1 in cells by using the mammalian two-hybrid assay and the co-immunoprecipitation assay, and verified that ZO-1 could interact with FHL1C through the PDZ domains of ZO-1. Moreover, with immunofluorescence staining, we found that FHL1C could induce ZO-1 translocating into nucleus. With a breast adenocarcinoma cell line MCF7, we showed that the interaction between FHL1C and ZO-1 could contribute to the epithelial-mesenchymal transition (EMT). Taken together, our study might provide new insight into the function of FHL1C on the regulation of EMT in cancer cells.

Macromolecular Bipill of Gemcitabine and Methotrexate Facilitates Tumor-Specific Dual Drug Therapy with Higher Benefit-to-Risk Ratio

The present study reports the synthesis, characterization, and biological evaluation of a novel macromolecular bipill, synthesized by appending two different anticancer agents, viz., gemcitabine (GEM) and methotrexate (MTX), to the distal ends of a long-circulating poly(ethylene glycol) (PEG) spacer. Covalent conjugation of GEM and MTX via PEG linker not only transformed the solubility profiles of constituent drug molecules, but significantly improved their stability in the presence of plasma. In vitro cytotoxicity studies confirmed that GEM-PEG-MTX exerts higher cytotoxicity (IC50 0.181 μM at 24 h) in human breast adenocarcinoma MCF-7 cell lines, when compared to free drug congeners, i.e., free GEM (IC50 0.294 μM at 24 h) and free MTX (IC50 0.591 μM at 24 h). Tumor growth inhibition studies in chemically induced breast cancer bearing rats established the superiority of GEM-PEG-MTX conjugate over all other pharmaceutical preparations including free drugs, physical mixture of GEM and MTX, and PEGylated GEM/MTX. Toxicity studies in tumor bearing rats as well as healthy mice corroborated that dual drug conjugation is an effective means to synergize the therapeutic indices of potential drug candidates while alleviating drug-associated side effects.

Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa

BackgroundBreast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.MethodsEADs was obtained from the root of D. suffruticosa by using sequential solvent extraction. Cytotoxicity was determined by using MTT assay, mode of cell death by cell cycle analysis and apoptosis induction by Annexin-FITC/PI assay. Morphology changes in cells were observed under inverted light microscope. Involvement of selected genes in the oxidative stress-mediated signaling pathway was explored using multiplex gene expression analysis.ResultsThe treatment of EADs caused cytotoxicity to MCF-7 cells in a dose- and time-dependent manner at 24, 48 and 72 hours with IC50 of 76 ± 2.3, 58 ± 0.7 and 39 ± 3.6 μg/mL, respectively. The IC50 of tamoxifen-treated MCF-7 cells was 8 ± 0.5 μg/mL. Induction of apoptosis by EADs was dose- and time- dependent. EADs induced non-phase specific cell cycle arrest at different concentration and time point. The multiplex mRNA expression study indicated that EADs-induced apoptosis was accompanied by upregulation of the expression of SOD1, SOD2, NF-κB, p53, p38 MAPK, and catalase, but downregulation of Akt1.ConclusionIt is suggested that EADs induced apoptosis in MCF-7 cells by modulating numerous genes which are involved in oxidative stress pathway. Therefore, EADs has the potential to act as an effective intervention against breast cancer cells.

Cobalt Complexes with Pyrazole Ligands as Catalyst Precursors for the Peroxidative Oxidation of Cyclohexane: X‐ray Absorption Spectroscopy Studies and Biological Applications

[CoCl(μ-Cl)(Hpz(Ph))3]2 (1) and [CoCl2(Hpz(Ph))4] (2) were obtained by reaction of CoCl2 with HC(pz(Ph))3 and Hpz(Ph), respectively (Hpz(Ph)=3-phenylpyrazole). The compounds were isolated as air-stable solids and fully characterized by IR and far-IR spectroscopy, MS(ESI+/-), elemental analysis, cyclic voltammetry (CV), controlled potential electrolysis, and single-crystal X-ray diffraction. Electrochemical studies showed that 1 and 2 undergo single-electron irreversible Co(II)→Co(III) oxidations and Co(II)→Co(I) reductions at potentials measured by CV, which also allowed, in the case of dinuclear complex 1, the detection of electronic communication between the Co centers through the chloride bridging ligands. The electrochemical behavior of models of 1 and 2 were also investigated by density functional theory (DFT) methods, which indicated that the vertical oxidation of 1 and 2 (that before structural relaxation) affects mostly the chloride and pyrazolyl ligands, whereas adiabatic oxidation (that after the geometry relaxation) and reduction are mostly metal centered. Compounds 1 and 2 and, for comparative purposes, other related scorpionate and pyrazole cobalt complexes, exhibit catalytic activity for the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone under mild conditions (room temperature, aqueous H2O2). In situ X-ray absorption spectroscopy studies indicated that the species derived from complexes 1 and 2 during the oxidation of cyclohexane (i.e., Ox-1 and Ox-2, respectively) are analogous and contain a Co(III) site. Complex 2 showed low in vitro cytotoxicity toward the HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma cell lines.

In vitro Antioxidant and Anticancer Properties of Active Compounds from Methanolic Extract of Pteris multifida Poir. Leaves

Aims: To isolate pure compounds from the methanolic fraction obtained from successive fractionation of defatted ethanolic extract and evaluate in vitro antioxidant and anticancer activity of the crude ethanolic extract, methanolic fraction and pure compounds isolated from methanolic fraction from leaves of Pteris multifida Poir. Study Design: Isolation and identification of the compounds, evaluation of antioxidant and anticancer activity on cervical cancer cell line (HeLa), lung carcinoma cell line (NCIH460) and breast carcinoma cell line (MCF-7). Place and Duration of Study: Vietnam Academy of Science and Technology of Ho Chi Minh City and School of Biotechnology, International University, Vietnam National University, Ho Chi Minh City, between December 2012 and September 2013. Methodology: The crude ethanolic leaf extract and methanolic fraction obtained from successive fractionation of defatted ethanolic extract from Pteris multifida leaves were prepared. The isolated compounds from methanolic fraction were identified using different spectroscopic techniques. Antioxidant activity of the samples was evaluated by using the stable free radical 2, 2diphenyl picrylhydrazyl (DPPH). Sulforhodamine B (SRB) assay was exploited for determination of anticancer activity against three selected human Original Research Article European Journal of Medicinal Plants, 4(3): 292-302, 2014 293 cancer cell lines: HeLa, NCI-H460 and MCF-7. Results: Two main compounds were isolated from methanolic fraction obtained from successive fractionation of defatted ethanolic extract: rutin (1) and apigenin-7-O-β-Dglucopyranoside (2). The crude ethanolic leaf extract showed weak antioxidant activity (IC50 = 89.84 μg/mL) whereas the methanolic fraction expressed quite strong antioxidant activity (IC50 = 21.9 μg/mL). Rutin (1) showed a good ingredient of antioxidant activity with IC50 value of 37.70 ± 0.03 μg/mL. Crude ethanolic leaf extract had cytotoxic activity against HeLa and NCI-H460 cell lines while the methanolic fraction had cytotoxic activity against HeLa, NCI-H460 and MCF-7 cell lines. Apigenin-7-O-β-D-glucopyranoside (2) had strong anticancer activity against MCF-7 cell line with IC50 = 22.62 ± 0.59 μg/mL. Conclusion: The crude ethanolic leaf extract and its methanolic fraction of P. multifida showed the potential activity in antioxidant and anticancer activity. Rutin had a potent antioxidant activity while apigenin-7-O-β-D-glucopyranoside had a strong anticancer activity against the human breast adenocarcinoma cell line MCF-7.

XIAP inhibitor and antiestrogen embelin abrogates metastasis and augments apoptosis in estrogen receptor positive human breast adenocarcinoma cell line MCF-7

Tamoxifen therapy for the treatment of hormone responsive breast cancer has limitations due to acquired resistance in the case of recurrences. Embelin, a known inhibitor of X-linked inhibitor of apoptosis protein (XIAP) was also reported to exhibit strong antiestrogenic effects in animal models. Dual role of embelin as a proapoptotic and antiestrogenic agent may have potential benefits in the therapy of breast cancer. In this study, the effects of embelin treatment on estrogen receptor positive Human breast adenocarcinoma (MCF-7) cells was investigated to primarily understand if embelin being an antiestrogen and XIAP inhibitor could be a potential alternative to tamoxifen therapy. Results revealed that, embelin at a concentration of 65μg/ml attenuated proliferation, inhibited metastatic migration, modulated the expression of Bcl2, Caspases and induced apoptosis in MCF-7 cells which was found to be p53 mediated. Hence, chemotherapy with embelin could be a promising strategy to be experimented in hormone responsive breast cancers.

In-vitro cytotoxicity study of methanolic fraction from Ajuga Bracteosa wall ex. benth on MCF-7 breast adenocarcinoma and hep-2 larynx carcinoma cell lines

Objective:Ajuga bracteosa Wall ex Benth (Labiatae) is popularly known in India as Neelkanthi. A decoction of the leaves, flowers, and barks is used in India for the treatment of cancer including diabetes, malaria, and inflammation etc. The main objective of this study is to investigate the cytotoxic potential of Ajuga bracteosa.Materials and Methods:Successive solvent extraction of Ajuga bracteosa in petroleum ether, methanol, and water extracts was done. These extracts were tested against human breast adenocarcinoma (MCF-7) and larynx carcinoma (Hep-2) tumor cell lines, using the thiazolyl blue test (MTT) assay.Results:The methanolic fraction of Ajuga bracteosa had shown the significant results against MCF-7 and Hep-2 tumor cell lines. The methanolic, petroleum ether and aqueous extract from Ajuga bracteosa, presented an IC50 value at 24 h of 10, 65, 70 μg/ml and 5, 30, 15 μg/ml on MCF-7 and Hep-2 cells, respectively. Steroids compounds namely β-sitosterol and unknown constituents were identified in the most active methanol extract of Ajuga bracteosa wall ex Benth. These known and unknown compounds exhibited cytotoxic potential against MCF-7 and Hep-2 cancer cells.Conclusion:Among all the tested extracts, methanolic extract can be considered as potential sources of anti-cancer compounds. Further studies are necessary for more extensive biological evaluations.

Lack of in vitro anticancer and antimicrobial activities in Suaeda maritima (seablite) crude extracts

Aims: The aim was to determine antimicrobial and anticancer activities for water and ethanol extracts of leaves and shooting parts of seablite. Materials and Methods: Anticancer activity tests of seablite extracts were performed by resazurin microplate assay (REMA) and tested with 3 cell lines including KB cell line, epidermoid carcinoma of the oral cavity (American Type Culture Collection [ATCC] CCL-17), MCF-7 cell line, breast adenocarcinoma (ATCC HTB-22) and NCI-H187 cell line, and small cell lung carcinoma (ATCC CRL-5804). Antimicrobial activities of seablite water and ethanol extracts against herpes simplex virus type-I (HSV-1) and Mycobacterium tuberculosis H 37 Ra strain were tested according by green fluorescent protein-based assay; Candida albicans (ATCC 90028) and Bacillus cereus (ATCC 11778 or TISTR 687) were tested according by REMA; and Plasmodium falciparum , K1 strain was tested according by micro-culture radioisotope techniques. Results: Both extracts were not possessed anticancer activity to KB-oral cavity cancer, MCF7-breast cancer and NCI-H187-small lung cancer cell lines at maximum concentration = 50 μg/mL. In the same way to anticancer activity assays, both extracts were not inhibited HSV-1, P. falciparum K1 strain, M. tuberculosis H 37 Ra strain and B. cereus at the same concentration. Conclusions: Ethanol and water extracts of leaves and shooting parts of seablite had no significant anticancer and antimicrobial activities.

The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well-known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6', 9', 1 and 7-positions, is described. In a previous study, replacement of the naturally occurring N-methyl group in the 6'-position with an N-ethylaminocarbonyl was shown to promote cell-cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9'-position, regioselective O-demethylation to reveal a free phenol in the 7-position, and reduction of the lactone to the corresponding cyclic ether in the 1-position. The incorporation of new aryl substituents in the 9'-position was also investigated. The study identified interesting new compounds able to induce G2/M cell-cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF-7, and the human pancreatic epithelioid carcinoma cell line PANC-1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6'-ethylaminocarbonyl along with 9'-chloro, 7-hydroxy and lactone moieties exhibited the most promising biological activities, with EC50 values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.

Cobalt(II) complexes with thiosemicarbazone as potential antitumor agents: synthesis, crystal structures, DNA interactions, and cytotoxicity

Two cobalt(II) complexes [Co(QCT)2]·Cl·1.5H2O (1) (QCT = quinoline-2-carboxaldehyde thiosemicarbazone) and [Co(QCMT)(CH3OH)Cl2] (2) (QCMT = quinoline-2-carboxaldehyde N4-methyl-thiosemicarbazone) have been synthesized and structurally characterized. Complex 1 crystallizes in a triclinic system with space group P–1 and complex 2 crystallizes in a monoclinic system with space group P2(1)/n. In both complexes the cobalt(II) center is six coordinated with distorted octahedral geometry. The interactions of two complexes with CT-DNA were investigated by electronic absorption spectra, circular dichroism (CD) spectra and fluorescence spectra. Results suggest that the complexes bind to DNA via groove binding mode, and complex 2 has stronger binding ability than complex 1. The in vitro cytotoxicity has been tested against the human lung adenocarcinoma cell line A-549, cisplatin-resistant cell line A-549/CDDP, and human breast adenocarcinoma cell line MCF-7. Complex 2 is more cytotoxic than complex 1, and both of them show higher cytotoxicity than the parent ligands alone. Compared with cisplatin, the two cobalt(II) complexes are more active against A-549/CDDP and MCF-7 cell lines at most experimental concentrations. Notably, although complex 2 is found to be less effective than cisplatin against the parent cell line A-549, it is much more effective than cisplatin against the resistant cell A-549/CDDP.

Synthesis of novel anticancer iridoid derivatives and their cell cycle arrest and caspase dependent apoptosis

Nyctanthes arbortristis Linn (Oleaceae) is widely distributed in sub-Himalayan regions and southwards to Godavari, India commonly known as Harsingar and Night Jasmine. In continuation of our drug discovery programme on Indian medicinal plants, we isolated arbortristoside-A (1) and 7-O-trans-cinnamoyl 6β-hydroxyloganin (2) from the seeds of N. Arbortristis, which exhibited moderate in vitro anticancer activity. Chemical transformation of 2 led to significant improvement in the activity in derivative 8 and 15 against HepG2 (human hepatocellular carcinoma), MCF-7 (breast adenocarcinoma) cell lines. The compounds 8 and 15 were also capable of cell cycle arrest and caspase dependent apoptosis in HepG2 cell lines. These iridoid derivatives hold promise for developing safer alternatives to the marketed drugs.

3,5,4′-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial–mesenchymal transition

The molecular basis of epithelial–mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4′-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of β-catenin, accompanied with the downregulation of β-catenin target genes and the increment of membrane-bound β-catenin. These results suggest the involvement of Wnt/β-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3β activity by inhibiting the phosphorylation of Akt, the event required for β-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, β-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells.