Human Breast Adenocarcinoma MCF-7 Cells Research Articles

Cytotoxic, anti-biofilm and antimicrobial polyketides from the plant associated fungus Chaetosphaeronema achilleae

From extracts of the plant associated fungus Chaetosphaeronema achilleae collected in Iran, a previously unreported isoindolinone named chaetosisoindolinone (1) and a previously undescribed indanone named chaetosindanone (2) were isolated in addition to five known metabolites, 2-(2-acetyl-3,5-dihydroxyphenyl) acetic acid (3), vulculic acid (4), 2-(2-acetyl-3-hydroxy-5-methoxyphenyl)acetic acid (5), curvulin (6), and curvulol (7). Their structures were elucidated on the basis of extensive spectroscopic analysis and high-resolution mass spectrometry. The isolated compounds were tested for their antimicrobial, anti-biofilm, and nematicidal activities. Compound 2 exhibited cytotoxicity against the human breast adenocarcinoma MCF-7 cells with an IC50 value of 1.5 μg/mL. Furthermore, compounds 4 and 7 almost completely inhibited biofilm formation in Staphylococcus aureus at 256 μg/mL. Weak antimicrobial activities were also observed for some of the isolated compounds against Mucor hiemalis, Rhodoturula glutinis, Chromobacterium violaceum, and Staphylococcus aureus.

Cytotoxic activity and volatile components of peel oil of Citrus volkameriana

Citrus volkameriana Pasq. (Family: Rutacea) is a very common edible and medicinal plant growing in several places in the world including Egypt. We previously studied the toxicity of components of the leaves; however, the peel oil has not been fully analyzed. In the current study, peel oil of C. volkameriana was prepared by hydro-distillation method, and was analyzed for its components using gas chromatography and gas chromatography–mass spectrometry. The recovered oil was formulated as oil in water emulsion using a wet gum technique with gum acacia as an emulsifier. Two compounds were selected from the identified oil components, emulsified using the same technique, and tested for their cytotoxicity along with the emulsified oil on five human tumor cell lines, as well as on one human non-tumorigenic epithelial breast cell line. Our results showed that limonene (68.5%) was found to be the major oil constituent, followed by γ-terpinene (11.3%). Other minor oil components include thymol methyl ether (4%), 4-terpineol (2.9%), cymol (2.4%) and α-pinene (2.1%). The oil showed a very strong cytotoxic effect on the five human tumor cells tested with the highest effect on human hepatoma HepG2 cells (IC50 = 0.038 μL/mL), followed by the effect on human laryngeal carcinoma HEp2 cells (IC50 = 0.045 μL/mL), human breast adenocarcinoma MCF7 cells (IC50 = 0.075 μL/mL), human lung carcinoma A549 cells (IC50 = 0.093 μL/mL), and human cervical cancer Hela cells (IC50 = 0.13 μL/mL). In contrast, the oil showed a lower cytotoxic effect on the non-tumorigenic breast MCF10A cells (IC50 = 0.106 μL/mL). D-limonene possessed similar cytotoxic results as the oil, suggesting a vital role in the cytotoxic effect obtained with the oil. Furthermore, α-pinene showed a strong cytotoxic effect on MCF7 cells (IC50 = 0.072 μL/mL) with a weaker effect on the MCF10A cells (IC50 = 0.185 μL/mL). In conclusion, Citrus volkameriana peel oil and its components have the potential to act as promising cytotoxic agents.

Synthesis and Cytotoxic Activity of New 1,3,4-Thiadiazole Thioglycosides and 1,2,3-Triazolyl-1,3,4-Thiadiazole N-glycosides.

New 1,3,4-thiadiazole thioglycosides linked to substituted arylidine systems were synthesized via glycosylation of the prepared 1,3,4-thiadiazole thiol compounds. Click strategy was also used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycosides by reaction of the acetylenic derivatives with different glycosyl azids followed by deacetylation process. The cytotoxic activities of the prepared compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds 2 and 3, the triazole glycosides linked to p-methoxyarylidine derivatives 14 and 15 in addition to the free hydroxyl glycoside 20 were found potent in activity comparable to the reference drug doxorubicin against MCF-7 human cancer cells. The acetylenic derivative 2 and glycoside 20 were also found highly active against HCT-116 cell lines.

Protective Effect of Obovatol Against MCF-7 Human Breast Adenocarcinoma Cells via Inducing Apoptosis and Cell Cycle Arrest

Protective Effect of Obovatol Against MCF-7 Human Breast Adenocarcinoma Cells via Inducing Apoptosis and Cell Cycle Arrest

Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors

Epidermal growth factor receptor (EGFR, also known as HER1) and HER2, prominent members of receptor tyrosine kinase (RTK) superfamily, have been reported as diagnostic or prognostic markers in tumor progression. Based on the importance of molecular hybridization of pyrazoline and thiazole scaffolds in the discovery of potent anticancer agents, new thiazolyl-pyrazoline derivatives (3a-v) were synthesized and screened for their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma and A375 human melanoma cell lines. 1-(4-(4-Fluorophenyl)thiazol-2-yl)-3-(4-morpholinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3c),1-(4-(4-cyanophenyl)thiazol-2-yl)-3-(4-morpholinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3f) and 1-(4-(4-cyanophenyl)thiazol-2-yl)-3-(4-piperidinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3q) were found as the most potent anticancer agents against A549 and MCF-7 cell lines compared to erlotinib. Compound 3q also showed moderate cytotoxic activity against A375 cell line. Moreover, these compounds exert a cancer cell–selective action against Jurkat cell line posing no toxicity on peripheral blood mononuclear cells (PBMCs). In order to enlighten the mechanism of action underlying anticancer activity, compounds 3c, 3f and 3q were investigated for their apoptotic effects on A549 and MCF-7 cell lines and inhibitory potencies against eight different RTKs including EGFR and HER2 compared to erlotinib. The results indicated that compounds 3f and 3q induced apoptosis in both cell lines and showed significant EGFR inhibitory activity with IC50 values of 4.34 ± 0.66 μM and 4.71 ± 0.84 μM, respectively when compared with erlotinib (IC50 = 0.05 ± 0.01 μM). Besides, compound 3f also inhibited HER2 notably with an IC50 value of 2.28 ± 0.53 μM making it a dual EGFR and HER2 inhibitor. Molecular docking studies, which were conducted to support the in vitro assays, pointed out that compound 3f showed high affinity into the ATP binding sites of EGFR and HER2.

Synthesis, characterization and evaluation of 1-monoacylglycerols of unsaturated fatty acids as potential bioactive lipids

The synthesis of 1-monoacylglycerols of selected unsaturated fatty acids and their antimicrobial and cytotoxicity activity is reported in the present study. The monoacylglycerols of fatty acids like undecenoic, oleic, linoleic and erucic acids were prepared by chemical esterification with solketal followed by deprotection. Fatty acids like alpha linolenic, gamma linolenic and ricinoleic acids were initially isolated from natural sources and further enriched in their respective methyl ester forms. The monoacylglycerols of ricinoleic and linolenic acid methyl esters were prepared by enzymatic transesterification with solketal using lipase from Candida antarctica followed by deprotection. The synthesized 1-monoacylglycerols were purified and characterized by spectral studies. The antimicrobial activity revealed that the monoacylglycerol of gamma linolenic acid was the most effective antibacterial followed by the monoacylglycerols of undecenoic and alpha linolenic acids. In the cytotoxicity assay against five cell lines, all the monoacylglycerols exhibited moderate activity but the activity was best against MCF7 Human Breast Adenocarcinoma cell lines.

Analysis and Identification of Active Compounds from Gami-Soyosan Toxic to MCF-7 Human Breast Adenocarcinoma Cells.

Gami-soyosan is a medicinal herbal formulation prescribed for the treatment of menopausal symptoms, including hot flashes and osteoporosis. Gami-soyosan is also used to treat similar symptoms experienced by patients with breast cancer. The incidence of breast cancer in women receiving hormone replacement therapy is a big burden. However, little is known about the components and their mechanism of action that exhibit these beneficial effects of Gami-soyosan. The aim of this study was to simultaneously analyze compounds of Gami-soyosan, and determine their cytotoxic effects on estrogen receptor (ER)-positive MCF-7 human breast adenocarcinoma cells. We established a simultaneous analysis method of 18 compounds contained in Gami-soyosan and found that, among the various compounds in Gami-soyosan, gallic acid (1), decursin (17), and decursinol angelate (18) suppressed the viability of MCF-7 cells. Gallic acid (1), decursin (17), and decursinol angelate (18) induced apoptotic cell death and significantly increased poly (ADP-ribose) polymerase (PARP) cleavage and the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) ratio. Decursin (17) increased the expression of cleaved caspases-8, -9, -7, and -3. Decursinol angelate (18) increased the expression of cleaved caspase-8 and -7. These three components altered the different apoptosis signal pathways. Collectively, gallic acid (1), decursin (17), and decursinol angelate (18) may be used to inhibit cell proliferation synergistically in patients with ER-positive breast cancer.

The cholesterol-derived metabolite dendrogenin A functionally reprograms breast adenocarcinoma and undifferentiated thyroid cancer cells

Dendrogenin A (DDA) is a tumor suppressor mammalian cholesterol-derived metabolite and a new class of ligand of the Liver X receptor (LXR), which displays tumor cell differentiation. In human MCF7 breast adenocarcinoma cells, DDA-induced cell differentiation was associated with an increased accumulation of neutral lipids and proteins found in milk indicating that DDA re-activates some functions of lactating cells. Active iodide transport occurs in the normal lactating mammary cells through the sodium/iodide symporter (NIS) and iodide (I) is secreted into milk to be used by the nursing newborn for thyroid hormones biosynthesis. In the present study, we assessed whether DDA may induce other characteristic of lactating cells such as NIS expression and iodine uptake in MCF7 breast cancer cells and extended this study to the papillary B-CPAP and undifferentiated anaplastic 8505c thyroid cancer cells. Moreover, we evaluated DDA impact on the expression of thyroid specific proteins involved in thyroid hormone biogenesis. We report here that DDA induces NIS expression in MCF7 cells and significantly increases the uptake of 131-I by acting through the LXR. In addition, DDA induces phenotypic, molecular and functional characteristics of redifferentiation in the two human thyroid carcinoma cell lines and the uptake of 131-I in the undifferentiated 8505c cells was associated with a strong expression of all the specific proteins involved in thyroid hormone biosynthesis, TSH receptor, thyroperoxidase and thyroglobulin. 131-I incorporation in the 8505c cells was stimulated by DDA as well as by the synthetic LXR ligand, GW3965. Together these data show that the re-differentiation of breast and thyroid cancer cells by DDA, is associated with the recovery of functional NIS expression and involves an LXR-dependent mechanism. These results open new avenues of research for the diagnosis of thyroid cancers as well as the development of new therapeutic approaches for radioiodine refractory thyroid cancers.

Micronuclei Elimination in MCF-7 Human Breast Adenocarcinoma Cells

t—Recent literature data have demonstrated that cells are able to eliminate micronuclei. Induction of micronuclei with antitubulin agents is widely used in antitumor therapy and elimination of micronuclei presumably facilitates the survival of tumor cells during therapy. In this regard, the investigation of micronuclei elimination has both fundamental and practical significance. In the present study, we show presence of two subpopulations of micronuclei (small single and large multiple micronuclei) in MCF-7 cells (human breast adenocarcinoma cell line, p53+) both in control and after paclitaxel treatment. Each of these subpopulations obviously has different mechanisms of formation. It has been shown that the lysosomal compartment can be involved in the elimination of micronuclei (for small micronuclei). It has been found that elimination of a micronucleus is a rare phenomenon. Most micronuclei were preserved, but the micronuclei could have morphological defects. We described different defects in a micronuclear envelope: lack of peripheral heterochromatin, swelling of the perinuclear space, micronuclear membrane breaks, and complete or partial absence of a nuclear lamina. We found the presence of p53-negative micronuclei. Lack of p53 activation is more characteristic for small single micronuclei. The obtained data allow us to conclude that the elimination of micronuclei cannot have a significant impact on the results of therapy. However, there is a danger of micronuclear cells progressing through the cell cycle (primarily for cells with small single micronuclei).

Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto‐plasmonic nanoparticles on MCF‐7 breast cancer cells

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). At the same time, thermometry was performed with an infrared (IR) camera. Then, the cells were exposed to 6 MV X-ray at various doses of 2 and 4 Gy. MTT (3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide) assay was performed to evaluate cell viability and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression ratio of Bax/Bcl2. Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The results obtained from MTT assay and qRT-PCR studies showed that NPs and RF hyperthermia had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and the level of apoptosis induction. A synergistic effect was also observed when the cancer cells were treated with a combination of NPs, RF hyperthermia, and RT. On the basis of the obtained results, it may be concluded that the use of magneto-plasmonic NPs in the process of hyperthermia and RT of cancer holds a great promise to develop a new combinatorial cancer therapy strategy.

Modulation of the solubility properties of arene ruthenium complexes bearing stannyl ligands as potential anti-cancer agents

Cleavage of the known ruthenium dimer [RuCl2(η6-C6H5OCH2CH2OH)]2 (1), bearing a hydrophilic substituent on the η6 coordinated aromatic ring, with the phosphine ligands: triphenyl phosphine, triphenyl phosphite, trimethyl phosphite, and 1,3,5-triaza-7-phosphaadamantane (PTA) afforded the known complexes [RuCl2(η6-C6H5OCH2CH2OH)(PPh3)] (2a), [RuCl2(η6-C6H5OCH2CH2OH){P(OPh)3}] (2b), [RuCl2(η6-C6H5OCH2CH2OH){P(OMe3)}] (2c), and [RuCl2 (η6-C6H5OCH2CH2OH)(PTA)] (4). The reaction of the known complex 2a with SnCl2 afforded, by facile insertion of the SnCl2 moiety into the RuCl bond, the novel complex [RuCl(η6-C6H5OCH2CH2OH)(PPh3)(SnCl3)] (3a). Similarly, the reaction of complex 2b with SnCl2 afforded the novel complex [RuCl(η6-C6H5OCH2CH2OH){P(OPh)3}(SnCl3)] (3b). Complexes 3a and 3b were fully characterized by spectroscopy (Infrared (IR) -spectroscopy, 1H, 31P and 119Sn Nuclear Magnetic Resonance (NMR) spectroscopy, UV–Vis spectroscopy and high resolution ESI-MS) and their thermal behaviour elucidated by Thermogravimetric Analysis (TGA). Density Functional Theory (DFT) calculations (Level of theory B3LYP, basis set for H, C, P, O, N and Cl is 6-31 + G (d,p) and for Ru and Sn is DGDZVP) for complex 3a, 3b and 4 were also carried out, in particular to elucidate the bonding situation between Ru and Sn in complexes. The hitherto unprecedented anti-cancer activity of the complexes 2a – 2c as well as the novel stannyl complexes 3a and 3b were evaluated against MCF-7 (oestrogen receptor positive) human breast adenocarcinoma cell lines. All complexes show activity active against MCF-7 cell lines, indicating potential application as an anti-tumor agent.

Activation of Autophagy and Nrf2 Signaling in Human Breast Adenocarcinoma MCF-7 Cells by Novel Monophenolic Antioxidants

The effect of novel water-soluble structurally related monophenolic compounds on the activity of two most important mechanisms of maintaining intracellular homeostasis, autophagy and the redox-sensitive signal system Keap1/Nrf2/ARE, has been studied in human breast adenocarcinoma cell line MCF-7 using confocal microscopy. Autophagy processes were analyzed on the basis of the amount of intracellular vesicles that were positive for the autophagy marker (LC3B). The activation of the Keap1/Nrf2/ARE system was determined by the translocation of the transcription factor Nrf2 into the nucleus. It was found that the effect of the tested compounds depended on their structure and concentration. When the inhibitor of autophagosome–lysosome fusion chloroquine was added to the culture medium (20 μM), the asymmetrically hindered by the tert-butyl group phenols with thiosulfonate (TS-13) and sulfonate group in the para-propyl substituent increased the rate of autophagosome elimination in MCF-7 cells. Shortening of the para-alkyl substituent by one methylene unit abolished the effect. The addition of the second ortho-tert-butyl substituent had the reverse result. Both tested compounds enhanced the translocation of the transcription factor Nrf2 into the nucleus of MCF-7 cells (which is a critical step in Keap1/Nrf2/ARE activation). It was observed after incubation with asymmetrically hindered by the tert-butyl group phenol with selenosulfonate group in para-propyl substituent (5−100 μM) for 4 h and with TS-13 (5−100 μM) for 24 h. Taking into account our previous findings on the toxicity of this group of compounds for MCF-7 cells we can conclude that these compounds exert different effect on autophagy and activation of the antioxidant response element signaling system Keap1/Nrf2/ARE.

4-O-Methylascochlorin inhibits the prolyl hydroxylation of hypoxia-inducible factor-1α, which is attenuated by ascorbate.

4-O-Methylascochlorin (MAC), a methylated derivative of ascochlorin, was previously shown to promote the accumulation of hypoxia-inducible factor (HIF)-1α in human breast adenocarcinoma MCF-7 cells. In the present study, we further investigated the effects of MAC on the expression and function of HIF-1α in human fibrosarcoma HT-1080 cells. MAC promoted the accumulation of the HIF-1α protein without affecting its constitutive mRNA expression and augmented the transcriptional activation of HIF target genes. Ascorbate, but not N-acetylcysteine, attenuated MAC-mediated HIF-1α accumulation. MAC-induced increases in HIF-1α transcriptional activity were also attenuated by ascorbate. MAC inhibited the hydroxylation of HIF-1α at the proline 564 residue, while it was reversed by ascorbate. MAC slightly decreased the intracellular concentration of ascorbate. The present results demonstrated that MAC promoted the accumulation of HIF-1α by preventing prolyl hydroxylation, and ascorbate attenuated the MAC-mediated inhibition of HIF-1α prolyl hydroxylation.

Synthesis and In Vitro Anticancer Activity of 6-Ferrocenylpyrimidin-4(3H)-one Derivatives.

Some ferrocenyl derivatives are active in vitro and in vivo against cancer. Generally, ferrocenyl derivatives for cancer research have three key components: a ferrocene moiety, a conjugated linker that lowers the oxidation potential and some derivative (peptide, nucleobase and others) that can interact with biomolecules. Since the pyrimidine fragment can easily pass through the membrane into the cells and become involved in metabolism; it appears to be promising. Furthermore, this fragment is an electron-acceptor group, so a spacer can be excluded. Therefore, the synthesis of 6-ferrocenylpyrimidin-4(3H)-one derivatives and the study of their anticancer activity have scientific and practical interest. The syntheses of 6-ferrocenylpyrimidin-4(3H)-one derivatives were performed by the condensation of ethyl 3-ferrocenyl-3-oxopropionate with thiourea or acetamidine or guanidine. The cytotoxicity of four 6- ferrocenylpyrimidin-4(3H)-one derivatives was evaluated by using the MTT assay in vitro against Human breast adenocarcinoma MCF-7 and normal human skin fibroblast HSF cells. The tested derivatives induced a concentration-dependent cytotoxic response in cell lines. A study of the cytotoxic activity of 6-ferrocenylpyrimidin-4(3H)-one derivatives by the MTT test has found that all compounds have a dose-dependent toxic effect on the lines of breast cancer cells (MCF-7) and normal human fibroblast cells (HSF). The most pronounced cytotoxic effect is exhibited by 2-methyl-6-ferrocenylpyrimidin- 4(3H)-one (MCF-7, IC50 17 ± 1 µM). The experimental results confirm the importance of investigation and design of ferrocenylpyrimidin- 4(3H)-one derivatives as anticancer agents. Compounds where the pyrimidine derivatives are directly linked to the ferrocene unit rather than via a spacer group also may be of interest for antiproliferative drug design.

Evidence for L-Dopa Decarboxylase Involvement in Cancer Cell Cytotoxicity Induced by Docetaxel and Mitoxantrone.

L-Dopa decarboxylase (DDC) expression has been implicated in the biochemistry of several human cancers. Docetaxel and Mitoxantrone are two widely used anticancer agents. Docetaxel is a semi-synthetic analogue of Paclitaxel, an extract from the bark of the rare Pacific yew tree Taxus brevifolia, and Mitoxantrone is an anthracenedione anticancer agent. The purpose of the present study was to investigate the effect of chemotherapeutic agents on the expression of human DDC in human prostate and human breast cancer cell lines. Furthermore, the study focused on the effect of chemotherapeutics - particularly Docetaxel and Mitoxantrone - on the viability of mammalian cells expressing human DDC protein isoforms. We investigated the effect of Docetaxel and Mitoxantrone on the expression of DDC in DU- 145 (androgen-independent prostate cancer cell line) and MCF-7 (human breast adenocarcinoma cell line). In order to gain insight into the effect of DDC on cell viability following chemotherapeutic agent treatment, we investigated the cytotoxicity and apoptosis levels on CHO cells expressing different human DDC protein isoforms. Our obtained data indicated that exposure of DU-145 and MCF-7 cells to Docetaxel and Mitoxantrone enhances the expression of neural type DDC mRNA isoforms. Interestingly, DDC protein levels were not affected, despite the cytotoxic events elicited by the chemotherapeutic agent treatment. Moreover, expression of DDC and its alternative protein isoforms, appear to enhance the cytotoxic and apoptotic events conferred by exposure to Docetaxel and Mitoxantrone. This study suggests the possible involvement of DDC expression in Docetaxel and Mitoxantrone- induced cytotoxicity and apoptosis.

Anti-proliferative and apoptotic effects of Rheum emodi on human breast adenocarcinoma, MCF-7 Cells, and antimicrobial effectiveness against selected bacterial strains

Background: Breast cancer is the most common gynecological malignancy and one of the leading causes of death in women worldwide. Since antiquity to date, the saga of usage of plants as medicines has been the mainstay among the people. In Ayurvedic and Unani systems of medicine, Rheum emodi (RE) commonly known as Revand chini or Rhubarb is an important medicinal plant. It is a perennial herb belonging to family Polygonaceae and has antimicrobial, anticarcinogenic, and anti-inflammatory properties. The rhizomes of RE have anthraquinone derivatives such as emodin, aloe-emodin, rhein, emodin glycoside, and chrysophanol glycosides. Objective: In this study, we have investigated the anti-cancerous potentials of RE ethanolic extract on human breast adenocarcinoma cells MCF-7 and its antimicrobial effect against selected pathogenic bacterial strains. Materials and Methods: The apoptotic and anti-proliferative potentials of RE on human breast adenocarcinoma cells MCF-7 were observed through cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT]), reactive oxygen species (ROS) generation, nuclear fragmentation, and mitochondrial membrane potential (MMP) analysis. Antimicrobial activity of RE was screened through well-diffusion assay. Results: The results show that RE significantly inhibits the proliferation and induces apoptosis in MCF-7 cells of breast adenocarcinoma in a dose-dependent manner. The MTT cellular viability assay and morphological study reveal that RE significantly induces morphological alterations in MCF-7 cells in a dose-dependent manner and thus inhibits cell proliferation. The cytotoxic effect of RE through the induction of apoptosis is evident by the disruption of MMP, nuclear fragmentation, and ROS accumulation. In addition, we have found that RE is potent enough to decrease the microbial activity of selective bacterial strains. Conclusion: The findings demonstrated that RE promotes significant apoptosis in breast adenocarcinoma MCF-7 cells. Therefore, RE may be a potent candidate that aids for adjuvant cancer treatment though further studies are needed to elucidate the comprehensive mechanistic pathways.

In vitro Evaluation of Antiproliferative, Lipoxygenase and Xanthine Oxidase Inhibitory Activities of Artemisia nilagirica (C.B.Clarke) Pamp. Leaf Extracts

The current study was performed to screen the extracts of Artemisia nilagirica (C.B. Clarke) Pamp. for antiproliferative and antiinflammatory properties. Antiproliferative activity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Antiinflammatory activity was evaluated in terms of lipoxygenase and xanthine oxidase inhibitory activities. Results indicated that out of the 3 extracts tested, methanol extract was found to inhibit Y79 (human retinoblastoma) and MCF-7 (human breast adenocarcinoma) cell lines. The same extract was also found to inhibit lipoxygenase and xanthine oxidase enzymes in a concentration-dependent manner with an IC50 of 128.20±3.39 and 144.23±2.04 μg/ml for lipoxygenase and xanthine oxidase, respectively. The present study highlighted the antiproliferative potential of the plant against cancer cell lines. The extracts inhibited lipoxygenase and xanthine oxidase enzymes. Therefore, this plant could be a valuable source for anticancer and antiinflammatory molecules.

Entosis and Cell Cycle in Tumor Cell Culture

Entosis is a type of cell cannibalism during which one tumor cell invades another. The fate of the inner cell can vary. It can leave the entotic vacuole, divide within it, or be subjected to lysosome-mediated degradation. The aim of our work was to determine whether MCF7 (p53+) human breast adenocarcinoma cells and A431 (p53-) human epidermoid carcinoma cells can pass through the cell cycle during entosis. The percentage of entotic cells was 1.01 ± 0.37% in MCF7 culture and 0.42 ± 0.27% in A431 culture. It was shown that inner cells, as well as outer cells, can synthesize DNA (BrdU incorporation) and enter mitosis. Morphometric analysis showed polyploidization of outer cells. This process is most pronounced in the A431 (p53–) cell line. In addition, polyploid cells may be the preferred targets of invasion in this culture. In the MCF-7 cell line, the number of G1-phase entotic cells was higher, probably due to p53-mediated cell cycle arrest or the preferred cell invasion in the G1-phase. Overall, in tumors with active p53 protein expression, the entosis contribution to polyploidy and genetic instability of tumor cells is less than in p53 tumor cells.

CYTOTOXIC ACTIVITY OF A MEDICINAL MANGROVE PLANT CERIOPS DECANDRA (GRIFF.) DING HOU LEAVES ON HUMAN BREAST ADENOCARCINOMA CELL LINE MCF-7

Objective: Ceriops decandra (Griff.) Ding Hou (Rhizophoraceae) is an evergreen mangrove tree widely used in folklore medicine for the treatment of several diseases. Concerning the presence of anticancer molecule in C. decandra, the present investigation was carried out to study the preliminary phytochemical screening, in vitro cytotoxic effect, and apoptotic induction of methanol extract of C. decandra.Methods: The preliminary phytochemical investigations were done using standard methods. Cytotoxic activity was analyzed in terms of brine shrimp (Artemia salina Leach) lethality bioassay. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay was used to evaluate the cell viability and growth inhibition of MCF-7 (human breast adenocarcinoma) cells after treatment with different doses of C. decandra extract. Cell morphological changes induced by the extract were observed using phase contrast inverted microscope. Induction of apoptosis was determined by DNA fragmentation assay.Results: Phytochemical screening revealed the presence of various potent phytochemicals. In the brine shrimp lethality bioassay, the LC50 of the extract was found to be 12.5 μg/mL, implying a promising cytotoxic effect. The MTT assay results showed increased inhibitory activity at a concentration-dependent manner and altered the cell morphology after exposure with C. decandra extract which exhibited typical apoptotic morphological changes. Furthermore, the characteristic DNA ladder pattern of C. decandra treated cells in agarose gel electrophoresis confirms the induction of apoptosis.Conclusion: The research revealed the cytotoxic effect of C. decandra on MCF-7 cells through its nature of induction of apoptosis.

Synthesis and biological evaluation of phthalocyanine-peptide conjugate for EGFR-targeted photodynamic therapy and bioimaging

To improve the biocompatibility and tumor selectivity, we employed an epidermal growth factor receptor (EGFR) binding peptide (namely GE11, with a sequence of Tyr-His-Trp-Tyr-Gly-Tyr-Thr-Pro-Gln-Asn-Val-Ile) as a tumor directing vector for the delivery of zinc(II) phthalocyanine for targeted photodynamic therapy and bioimaging. The photophysical properties, cellular uptake, in vitro cytotoxicity, and in vivo biodistribution of this phthalocyanine-peptide conjugate (namely Pc-GE11) have been evaluated. Pc-GE11 exhibited higher cellular uptake on EGFR-overexpressing epidermoid carcinoma A431 cells when compared with that on human breast adenocarcinoma MCF7 cells (low EGFR expression). Moreover, pretreatment of A431 cells with GE11 peptide inhibited the cellular uptake of Pc-GE11 significantly and it exhibited exclusive light-activated cytotoxicity toward A431 cells. Furthermore, Pc-GE11 showed much higher tumor accumulation than the non-targeted control compound containing a random peptide sequence (Tyr-Trp-Gly-Pro-Asn-Ile-His-Tyr-Tyr-Thr-Gln-Val) after intravenous administration in A431-tumor bearing mice, indicating the potential application of this GE11 peptide-conjugated photosensitizer for targeted photodynamic therapy and bioimaging.