Michigan Cancer Foundation-7 Cells Research Articles

Highly efficient and simultaneous production of thirteen taxanes from Taxus × media and mining of their new bioactivity

Taxus serves as a primary natural source of paclitaxel, a valuable anticancer drug. Developing an efficient and synchronous separation and purification process for the abundant taxanes in Taxus, as well as mining their potential bioactive, can not only improve the production efficiency of paclitaxel but also further reduce the production cost. In this study, the abundant taxanes in the leaves and branches of Taxus × media, as well as the intermediates obtained during the purification process, were analyzed by high-performance liquid chromatography (HPLC) in combination with high-resolution accurate-mass spectrometry (LC-HR-MS/MS). Subsequently, thirteen taxanes were successfully separated and purified to a purity of over 98% with a recovery rate of 61% in a pilot-scale production. Notably, the purity and recovery of paclitaxel were increased to over 99.2% and 78.2%, respectively. Interestingly, taxuspine M was identified for the first time to exhibit superior binding properties with poly ADP-ribose polymerase 1 (PARP1) and NRH:quinone oxidoreductase 2 (NQO2) proteins, which were highly associated with breast cancer, through virtual screening across the human disease therapeutic protein in the therapeutic target database (TTD). Moreover, taxuspine M demonstrated significant anti-proliferative ability against the Michigan Cancer Foundation-7 (MCF-7) cell line with an IC50 value of 195.5 nM, indicating its potential as an anticancer agent. This study provides an improved scalable process for the highly efficient and comprehensive utilization of plant-source pharmaceutical resources.

Synthesis of Zeolitic imidazolate frameworks-8@ layered double hydroxide polyhedral nanocomposite with designed porous voids as an effective carrier for anti-cancer drug-controlled delivery.

In nanotechnology, compounds containing metal materials are used in pharmaceutical sciences. The main purpose of this research was to introduce a novel method to control the amount of zeolite imidazolate framework (ZIF) in water by forming a protective layer such as layered double hydroxide (LDH). Firstly, ZIF was synthesised as the nucleus of the nanocomposite, and then LDH was formed by in situ synthesis as a protective layer. Scanning electron microscope, Fourier-transform infrared spectroscopy, X-Ray Diffraction, and Brunauer, Emmett and Teller techniques were used to determine (ZIF-8@LDH chemical structure and morphology. Our findings revealed that the ZIF-8@LDH-MTX complex could interact with carboxyl groups and trivalent cations by creating a bifurcation bridge, clarity, and high thermal stability. The antibacterial test indicated that ZIF-8@LDH was able to inhibit pathogenic growth. 2,5-Diphenyl-2H-Tetrazolium Bromide assay results showed that ZIF-8@LDH alone had no notable cytotoxic effect on Michigan Cancer Foundation-7 (MCF-7) cancer cells. However, the cytotoxicity rate was significantly increased in treated MCF-7 cells with ZIF-8@LDH-MTX compared to that of treated cells with methotrexate alone, which can be reasoned by the protection of drug structure and increasing its permeability. The drug release profile was constant at pH=7.4. All findings indicated that the ZIF-8@LDH complex could be considered a newly proposed solution for effective anti-cancer drug delivery.

Efficacy of resveratrol against breast cancer and hepatocellular carcinoma cell lines.

To evaluate the anti-cancer effect of resveratrol on Michigan cancer foundation-7 (MCF-7) and hepatoblastoma cell line (HepG2) cells. The study was carried out at the Department of Botany and Microbiology, Prince Sattam bin Abdulaziz University, Al-kharj, Saudi Arabia, from August 2022 to October 2022. Different concentrations of resveratrol were added to the MCF-7 and HepG2 cell lines. Cell death and proliferation were measured with MTT and Trypan blue exclusion assays. Apoptosis markers were assessed by using a quantitative PCR assay (qPCR). The resveratrol was shown to suppress the proliferation of MCF-7 and HepG2 cells at dose- and time-dependent. The cytotoxic effect of resveratrol was observed even at 100 μM after 24 hours. In comparison to untreated cells, resveratrol treatment reduced the viability of MCF-7 cells to roughly 57.5% with a half maximal inhibitory concentration (IC50) of 51.18 μM and HepG2 cells to 56.2% with an IC50 of 57.4 μM. Furthermore, in the tested cell lines, resveratrol was able to induce apoptosis mediated by elevated apoptosis markers. Resveratrol appears to be an excellent candidate agent in anticancer therapy in various human cancers.

Repeated exposure to 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) accelerates ligand-independent activation of estrogen receptors in long-term estradiol-deprived MCF-7 cells

It was previously identified that there may be an active metabolite of bisphenol A (BPA), 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP). An in vitro system was developed to detect MBP toxicity to the Michigan Cancer Foundation-7 (MCF-7) cells that had been repeatedly exposed to a low dose of the metabolite. MBP profoundly activated estrogen receptor (ER)-dependent transcription as a ligand, with an EC50 of 2.8 nM. Women are continuously exposed to numerous estrogenic environmental chemicals; but their susceptibility to these chemicals may be significantly altered after menopause. Long-term estrogen-deprived (LTED) cells, which display ligand-independent ER activation, are a postmenopausal breast cancer model derived from MCF-7 cells. In this study, we investigated the estrogenic effects of MBP on LTED cells in a repeated exposure in vitro model. The results suggest that i) nanomolar levels of MBP reciprocally disrupt the balanced expression of ERα and ERβ proteins, leading to the dominant expression of ERβ, ii) MBP stimulates ERs-mediated transcription without acting as an ERβ ligand, and iii) MBP utilizes mitogen-activated protein kinase and phosphatidylinositol-3 kinase signaling to evoke its estrogenic action. Moreover, the repeated exposure strategy was effective for detecting low-dose estrogenic-like effects caused by MBP in LTED cells.

Synthesis and biological evaluation of benzamide-chalcone hybrids as potential c-Metkinase and COX-2 inhibitors.

c-Met kinase and cyclooxygenase 2 (COX-2) enzymes are two significant targets in tumor progression. Chalcone and benzamide moieties were combined using molecular hybridization to assess their potential as c-Met kinase and COX-2 inhibitors. 4-Methylbenzamide and 4-chlorobenzamide chalcone analogs were synthesized, characterized, and evaluated for antiproliferative activity on Michigan Cancer Foundation-7 (MCF-7), HT-29, MDA-MB-231, COLO-205, and A549 cell lines by sulforhodamine-B stain (SRB) assay. Following the SRB assay, compounds were evaluated for their c-Met kinase and COX-2 inhibitory potential. All compounds inhibited COX-2 with half-maximal inhibitory concentration (IC50 ) <10 µM. Compounds 7h, 7i, 7j, 8f, and 8j inhibited c-Met with IC50 <10 µM. Compound 7h was evaluated for its long-term antiproliferative and anti-migratory effects by colony formation and wound healing assay. It exerted these effects in a concentration-dependent manner. Compounds 7j and 8j were further evaluated for in vitro antiangiogenic effects. Compound 7j exhibited moderate antiangiogenic effect while compound 8j exhibited strong effect. Compounds 7h, 7i, 7j, 8f, and 8j were evaluated for the serum protein binding, using the in vitro bovine serum albumin binding assay. The results indicated that the tested compounds bind to bovine serum albumin (BSA) and can be further explored by other studies.

The oncogenic and immunological roles of histidine triad nucleotide-binding protein 1 in human cancers and their experimental validation in the MCF-7 cell line.

Histidine triad nucleotide binding protein 1 (HINT1) is a haplo-insufficient tumor suppressor gene that plays a significant role in cell proliferation and survival. However, to date, no systematic pan-cancer analysis has been conducted to explore its function in prognosis, and its oncogenic and immunological roles. We also analyzed the role of HINT1 in breast cancer (BC) progression in vitro. An analysis of the HINT1 expression pattern was performed using the TIMER database. The infiltration of immune cells into several cancer types was also studied using the Xena Shiny tool. To determine the relationship between stemness and the expression of HINT1 mRNA, the Spearman correlation test was used with the SangerBox tool. The correlation between HINT1 and functional states in various cancers was determined from the CancerSEA database. The potential role of HINT1 in BC oncogenesis was also investigated by Western blot and Annexin V/PI assays. The Cancer Genome Atlas pan-cancer data analysis suggested that HINT1 was extensively altered in most tumor tissues but not in most adjacent normal tissues. A high expression of HINT1 was associated with the decreased infiltration of cluster of differentiation (CD)4+ T cells. Importantly, increased HINT1 expression was also associated with a large majority of tumors with high stemness and lower stromal, immune, and estimate scores. Further, the expression of HINT1 was significantly associated with the tumor mutational burden (TMB) and microsatellite instability (MSI) in certain tumor types. Finally, HINT1 overexpression was found to impair BC progression by promoting cell apoptosis. HINT1 upregulation also reduced the expression of microphthalmia transcription factor (MITF) and β-catenin in BC Michigan Cancer Foundation-7 (MCF-7) cells, and the phosphorylation of protein kinase B (p-Akt). The present study showed that HINT1 plays an oncogenic role in various cancers and could also be used as a biomarker for BC.

Comparison of translational and rotational modes towards passive rheology of the cytoplasm of MCF-7 cells using optical tweezers.

A colloidal particle placed inside the cell cytoplasm is enmeshed within a network of cytoskeletal fibres immersed in the cytosolic fluid. The translational mode is believed to yield different rheological parameters than the rotational mode, given that these modes stretch the fibers differently. We compare the parameters for Michigan Cancer Foundation-7 (MCF-7) cells in this manuscript and find that the results are well comparable to each other. At low values of 0 Hz viscosity, the rotational and translational viscoelasticity matches well. However, discrepancies appear at higher values which may indicate that the cytoskeletal modes involved in rotation and translation of the particle are getting invoked. We also show that the 0 Hz viscosity increases as the cell ages under the conditions of constant room temperature of 25°C on the sample chamber.

Structure-activity relationship study to improve cytotoxicity and selectivity of lonafarnib against breast cancer cells.

Lonafarnib is designed as a farnesyltransferase (FTase) inhibitor and displays inhibitory activities against a wide range of tumor cells. However, a major disadvantage is its unselective activity and high cytotoxicity against nonmalignant cells. Therefore, we structurally modified the terminal 4-methylpiperidine-1-carboxamide residue of lonafarnib and evaluated the antiproliferative effects of the resulting derivatives in Michigan Cancer Foundation - 7 (MCF-7) breast cancer cells as well as simian virus 80 (SV-80) fibroblasts. The highest cytotoxicity against both cell lines (IC50 about 2 µM) was shown by the piperidin-4-yl carbamate 15i and the S-(piperidin-4-yl) carbamothioate 15j. Selectivity for tumor cells was realized in the case of the 1-cyclohexyl-1-methylurea derivative 15b. It reduced the growth of MCF-7 cells with an IC50 of 11.4 µM (lonafarnib: IC50 = 10.8 µM) without influence on the growth of SV-80 cells (IC50 > 50 µM; lonafarnib: IC50 = 14.0 µM). Molecular modeling studies were performed to correlate the cytotoxicity with possible FTase interactions. The theoretical investigations, however, documented a comparable attachment of active, less active, and inactive compounds and did not allow an interpretation of the biological results based on these theoretical considerations.

Titanium Culture Vessel Presenting Temperature Gradation for the Thermotolerance Estimation of Cells.

Hyperthermia can be induced to exploit the thermal intolerance of cancer cells, which is worse than that of normal cells, as a potential noninvasive cancer treatment. To develop an effective hyperthermia treatment, thermal cytotoxicity of cells should be comprehensively investigated. However, to conduct such investigations, the culture temperature must be accurately regulated. We previously reported a culture system in which the culture temperature could be accurately regulated by employing metallic culture vessels. However, appropriate temperature conditions for hyperthermia depend on the cell species. Consequently, several experiments need to be conducted, which is a bottleneck of inducing hyperthermia. Hence, we developed a cell culture system with temperature gradation on a metallic culture surface. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used as cancer and normal cell models, respectively. Normal cells showed stronger thermal tolerance; this was because the novel system immediately exhibited a temperature gradation. Thus, the developed culture system can be used to investigate the optimum thermal conditions for effective hyperthermia treatment. Furthermore, as the reactions of cultured cells can be effectively assessed with the present results, further research involving the thermal stimulation of cells is possible.

Study on the mechanism of cholic acid derivatives in traditional Chinese medicine based on the regulation of gene expression

To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine (TCM) based on the regulation of gene expression. Genome-wide gene expression profiles of Michigan Cancer Foundation-7 (MCF-7) cells treated with or without 4 cholic acid derivatives were detected by gene chip technology. Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map (CMap) database. The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking. The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database, and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Compared with the reference genome in the CMap database, the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic, anticancer, anti-inflammatory, and anti-infective drugs. Among them, 4 derivatives were associated with antianxiety drugs, and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gamma-aminobutyric acid (GABA) receptors. Moreover, the cytoskeletal pathway is one of the pathways enriched in the derivatives. Of them, ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells. The gene expression detection method, combined with CMap and pathway enrichment analysis, could be used to study the mechanism of the active ingredients of TCM. In addition, our research showed that cholic acid derivatives have a potential affinity for membrane receptors, where they can exert anxiolytic activity by modulating opioid receptor, GABA receptor, and dopamine receptor. Moreover, ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation, probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.

Solubility Enhancement of Anticancer Drug Belinostat via the Co-crystallization Strategy: Synthesis, Characterization, and Antitumor Activity In Vitro Evaluation

Belinostat (PXD101), a biopharmaceutical classification system II (BCSII) drug approved for treating refractory T-cell lymphoma, is currently administered by intravenous injection. To improve patient compliance, the development of oral formulations of PXD101 has attracted attention. Because the solubility and dissolution rate of active pharmaceutical ingredients can affect the therapeutic effect of the oral formulations, this work explores solid-state form modification of PXD101 by co-crystallization with four coformers, namely, theophylline, isonicotinamide (INA), isoniazid (INH), and l-proline (l-Pro) to solve the problem of poor water solubility. The four cocrystals were obtained on the basis of N–H···O, O–H···O, and O–H···N synthons. All the four obtained multicomponent crystals were characterized by powder X-ray diffraction (PXRD) and thermal analysis, meanwhile, crystal structure determination was performed by single-crystal XRD. The results of CrystalCMP show the similar packing patterns of PXD101-INA and PXD101-INH cocrystals. The data analysis from powder dissolution experiments suggested that the apparent solubility of the obtained multicomponent crystals is 1.14–2.22 times more than that of PXD101, and PXD101-l-Pro shows a completely different dissolution behavior from that of the other three cocrystals. Finally, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay experiments demonstrated that the PXD101-INA cocrystal can significantly inhibit the proliferation of Michigan Cancer Foundation-7 (MCF-7) cells even at a low concentration (0.01 μM). Such results shed light on the potential value of multicomponent crystals in the further development of pharmaceutical products.

Yanghe decoction attenuated pain hypersensitivity induced by michigan cancer foundation-7 injection in rats with bone metastases from breast cancer by inhibiting transient receptor potential ankyrin 1.

To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7 (MCF-7). Bone pain was induced in the tibia of rats injected with MCF-7 cells. The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats. The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency. Liquid chromatography-mass spectrometry, Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunohistochemical (IHC) staining were performed for analysis. Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1 (TRPA1) inhibitor. In morphology study, Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group. Furthermore, Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level. Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis, and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-α and interleukin-6, interleukin-1 beta by ELISA. As the cytochromec oxidase subunit II/prostaglandin E2 (PGE2) is required for cancer development, Yanghe decoction reduced the expression of PGE2 in the tissue and serum. Taken together, Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.

Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli.

Opioid receptors are naloxone-sensitive (MOP [mu: μ], DOP [delta: δ], and KOP [kappa: κ]) and naloxone-insensitive Nociceptin/Orphanin FQ (N/OFQ) peptide receptor (NOP). Clinically, most opioid analgesics target MOP. Angiogenesis is the formation of new blood vessels and involves endothelial cell activation, proliferation, and migration. The effect of opioids on this process is controversial with no data for NOP receptor ligands. We used patient-derived human umbilical vein endothelial cells (HUVECs) treated with media from the Michigan Cancer Foundation-7 (MCF-7) breast cancer cells or vascular endothelial growth factor (VEGF; 10 ng ml-1) and fibroblast growth factor (FGF; 10 ng ml-1) as angiogenic stimuli. We have measured (i) NOP/MOP messenger RNA, (ii) receptor protein using N/OFQATTO594 and DermorphinATTO488 as fluorescent probes for NOP and MOP, and (iii) NOP/MOP function in a wound healing assay (crude measure of migration that occurs during angiogenesis). HUVEC lines from 32 patients were used. Using all 32 lines, mRNA for NOP but not MOP was detected. This was unaffected by media from MCF-7 cells or VEGF/FGF. There was no binding of either N/OFQATTO594(NOP) or DermorphinATTO488(MOP) in the absence or presence of angiogenic stimuli (six lines tested). In the absence of MOP mRNA, this was expected. Whilst MCF-7 conditioned medium (not VEGF/FGF) reduced wound healing per se (14 lines tested), there was no effect of N/OFQ (NOP ligand) or morphine (MOP ligand). Media from MCF-7 breast cancer cells or VEGF/FGF as angiogenic stimuli did not influence NOP translation into receptor protein. MOP was absent. In the absence of constitutive or inducible MOP/NOP, there was no effect on wound healing as a measure of angiogenesis.

The in-vitro proliferation-suppression of MCF-7 and HeLa cell lines mediated by differently substituted ionic phthalocyanines in sonodynamic therapy supplemented-photodynamic therapy

This work focuses on the study of the effects of the ultrasonic frequency (MHz) and power (W.cm−2) on the stability, reactive oxygen species yields and cytotoxicity activities of differently substituted ionic phthalocyanines (Pcs) in sonodynamic therapy (SDT). Four ultrasonic parameters were investigated: Par I (1 MHz: 1 W.cm−2), Par II (1 MHz: 2 W.cm−2), Par III (3 MHz: 1 W.cm−2) and Par IV (3 MHz: 2 W.cm−2). A higher degradation of the Pcs was observed with increasing power at the Par II. Two reactive oxygen species (ROS) were detected in the ultrasound treated Pcs: singlet oxygen and hydroxyl radicals. Due to minimal degradation of most Pcs, Par I was chosen for SDT, photodynamic therapy (PDT), and photo-sonodynamic therapy (PSDT) against Michigan Cancer Foundation-7 and Henrietta Lacks cancer cell lines. PSDT generally showed improved therapeutic efficacies of the Pcs compared to the SDT and PDT mono treatments.

A hypoxia responsive silicon phthalocyanine containing naphthquinone axial ligands for photodynamic therapy activity

A liposome loaded‑silicon (IV) phthalocyanine (SiPc) containing naphthoquinone axial ligands as hypoxia-responsive a prodrug-like moieties (Prodrug-SiPc), is herein reported. With the help of computational methods, this study assessed the photophysical, photochemical and electrochemical redox properties of the Prodrug-SiPc to elucidate the relationship between material structure and properties. The attachment of the axial quinoid moieties endowed the Prodrug-SiPc with Type I/II photochemical and prodrug-like properties. Following liposomal encapsulation, the therapeutic efficacy of Prodrug-SiPc-liposomes was investigated against Michigan Cancer Foundation-7 (MCF-7) and Henrietta Lacks (Hela) cancer cells as in vitro cancer models and revealed that the as-synthesized Prodrug-SiPc-liposomes are potential photodynamic therapy (PDT) drug candidates. The Prodrug-SiPc-liposome takes full advantage of the hypoxic microenvironment of tumors - a side effect PDT - to trigger therapy, resulting in significantly enhanced efficacy compared to typical PDT. This work highlights the importance of multiple characteristics in designing new and effective photosensitizer candidates.

Anisotropic 3D confinement of MCF-7 cells induces directed cell-migration and viscoelastic anisotropy of cell-membrane

Tumor-associated collagen signature-3 (TACS-3) is a prognostic indicator for breast cancer survival. It is characterized by highly organized, parallel bundles of collagen fibers oriented perpendicular to the tumor boundary, serving as directional, confining channels for cancer cell invasion. Here we design a TACS-3-mimetic anisotropic, confined collagen I matrix and examine the relation between anisotropy of matrix, directed cellular migration, and anisotropy of cell membrane-the first direct contact between TACS-3 and cell-using Michigan Cancer Foundation-7 (MCF-7) cells as cancer-model. Using unidirectional freezing, we generated ∼50 μm-wide channels filled with collagen I. Optical tweezer (OT) microrheology shows that anisotropic confinement increases collagen viscoelasticity by two orders of magnitude, and the elastic modulus is significantly greater along the direction of anisotropic confinement compared to that along the orthogonal direction, thus establishing matrix anisotropy. Furthermore, MCF-7 cells embedded in anisotropic collagen I, exhibit directionality in cellular morphology and migration. Finally, using customized OT to trap polystyrene probes bound to cell-membrane (and not to ECM) of either free cells or cells under anisotropic confinement, we quantified the effect of matrix anisotropy on membrane viscoelasticity, both in-plane and out-of-plane, vis-à-vis the membrane. Both bulk and viscous modulus of cell-membrane of MCF-7 cells exhibit significant anisotropy under anisotropic confinement. Moreover, the cell membrane of MCF-7 cells under anisotropic confinement is significantly softer (both in-plane and out-of-plane moduli) despite their local environment being five times stiffer than free cells. In order to test if the coupling between anisotropy of extracellular matrix and anisotropy of cell-membrane is regulated by cell-cytoskeleton, actin cytoskeleton was depolymerized for both free and confined cells. Results show that cell membrane viscoelasticity of confined MCF-7 cells is unaffected by actin de-polymerization, in contrast to free cells. Together, these findings suggest that anisotropy of ECM induces directed migration and correlates with anisotropy of cell-membrane viscoelasticity of the MCF-7 cells in an actin-independent manner.

Evaluation of the Role of Merromoside from Ipomoea aquatica Forsskal Hydroalcoholic Extract in the Downregulation of ROS Species in Overcoming MDR in Breast Cancer.

The medicinal plant Ipomoea aquatica belonging to convulvulaceae family is an effective natural herb for treatment of various ailments and possesses effective anticancer activity. The aim of the work is to characterize a secondary metabolite merromoside (a resin glycoside) for anti-breast cancer activity through down regulation of ROS species. The Extract of the whole plant has been prepared by maceration method using 50%v/v ethanol in distilled water to get a hydroalcoholic extract. The phytochemical evaluation reveals that the active secondary metabolite was isolated by using column chromatographic technique. The isolated compound was evaluated for its anticancer properties through invitro method such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on Michigan Cancer Foundation-7 Cell lines. The purity and structural characterization were done by high-performance thin layer chromatography, Fourier Transform Infrared Spectroscopy, Proton and13C Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography-Mass Spectrometry. The isolated compound (W04) from the derived extract showed Rf value of 0.79 that showed IC50 of 182.8μg/ml. The chemical structure of W04 has been confirmed as [4,5-dihydroxy-6-[5-hydroxy-2-methyl-4-(2-methylpropanoyloxy)-6-[(24,25,26-trihydroxy-5,23-dimethyl-9-oxo-19-pentyl-2,4,8,20,22-pentaoxatricyclo[19.2.2.13,7]hexacosan-6-yl)oxy]oxan-3-yl]oxy-2-methyloxan-3-yl] 2-methyl propanoate with the molecular weight of 979.15268. The isolated compound merromoside from hydroalcoholic extract of Ipomoea aquatica has been evaluated for anti-breast cancer properties. The down regulation of ROS species will prevent reverse signalling and angiogenesis. This indicates that merromoside will overcome MDR in breast cancer especially DOX-resistant.

Methotrexate loaded in alginate beads for controlled drug release against breast cancer

Methotrexate (MTX), as a folate antagonist is used for breast cancer chemotherapy, but its application due to the adverse side effects was limited. In this study, MTX were encapsulated in magnetic alginate beads coated with glutaraldehyde to control its release in order to reduce the side effects and improve its stability. The complex was characterized by physicochemical studies. The encapsulation efficiency was 75 % and the complex showed acceptable controlled release behavior. The cell cytotoxicity assessed using methylthiazol tetrazolium (MTT) method showed that magnetic alginate beads-MTX, in lower dosage has higher anticancer effect compared to the free MTX. The real-time polymerase chain reaction (PCR) was used to evaluate apoptotic factors Bcl2 associated X gene (Bax), B-cell lymphoma 2 (Bcl-2), and neuroinflammatory marker tumor necrosis factor-alpha (TNF-α) genes expression level on the treated cells. The findings demonstrated the significant increase of expression of Bax and a significant decrease in the expressions of Bcl-2 and TNF-α in Michigan cancer foundation-7 (MCF-7) cells. These results indicated that the developed drug can overcome the side effects of MTX and offer a controlled drug release for a sustained period with the long-term treatment of breast cancer.

Nanomolar activity of 4-hydrazinylphenyl benzenesulfonate against breast cancer Michigan Cancer Foundation-7 cell lines.

Hydrazine is an alkaline reduction compound which is widely used in synthesis. Based on the structure-activity analysis, to elicit antitumor activity, the presence of the N-methyl group is an absolute requirement. The aim of the research is to synthesize a new hydrazine derivate compound that has potency as a novel anti-breast cancer. 4-hydrazinylphenyl benzenesulfonate was synthesized employing reduction and diazotization methods. Structure characterization was carried out using Fourier transform infrared (FTIR), C13-nuclear magnetic resonance (NMR), H1-NMR, and High Resolution Time-of-Flight Mass Spectrometry (HR-TOF-MS). The anti-cancer activity of this compound against breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line was determined using a PrestoBlue viability assay. The new of hydrazine derivative, 4-hydrazinylphenyl benzenesulfonate, has been successfully synthesized. The reduction and diazotization methods have been successfully used in the synthesis of new compound of hydrazine derivatives. Structure characterization of 4-hydrazinylphenyl benzenesulfonate was established using FTIR, C13-NMR, H1-NMR, and HR-TOF-MS. The anti-cancer activity of this compound against breast cancer MCF-7 cell line was determined using a PrestoBlue viability assay with IC50 0.00246 μg/mL or 9.32 nM. In conclusion, 4-hydrazinylphenyl benzenesulfonate was successfully synthesized as a new candidate for anti-breast cancer compound.

Enhanced mitochondria destruction on MCF-7 and HeLa cell lines in vitro using triphenyl-phosphonium-labelled phthalocyanines in ultrasound-assisted photodynamic therapy activity.

This work reports on the reactive oxygen species (ROS) generation and the therapeutic activities of new triphenyl-phosphonium-labelled phthalocyanines (Pcs), the 2,9,16,23-tetrakis(N-(N-butyl-4-triphenyl-phosphonium)- pyridine-4-yloxy) Zn(II) Pc (3) and 2,9,16,23-tetrakis-(N-(N-butyl-4-triphenyl-phosphonium)-morpholino) Zn(II) Pc (4) upon exposure to light, ultrasound and the combination of light and ultrasound. Two types of ROS were detected: the singlet oxygen (1O2) and hydroxyl radicals. For light irradiations, only the 1O2 was detected. An increase in the ROS generation was observed for samples treated with the combination of light and ultrasound compared to the light and ultrasound mono-treatments. The in vitro anticancer activity through photodynamic (PDT) and sonodynamic (SDT) therapy for the Pcs were also determined and compared to the photo-sonodynamic combination therapy (PSDT). The two cancer cell lines used for the in vitro studies included the Michigan Cancer Foundation-7 (MCF-7) breast cancer and Henrietta Lacks (HeLa) cervical cancer cell lines. The SDT treatments showed improved therapeutic efficacy on the cancer cells for both the Pcs compared to PDT. PSDT showed better therapeutic efficacy compared to both the PDT and SDT mono-treatments.