Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.

Download Full-text

The Impact of Antioxidants from the Diet on Breast Cancer Cells Monitored by Raman Microspectroscopy

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180502120804 ◽

2018 ◽

Vol 16 (2) ◽

pp. 127-137

Author(s):

Paula Sofia Coutinho Medeiros ◽

Ana Lúcia Marques Batista de Carvalho ◽

Cristina Ruano ◽

Juan Carlos Otero ◽

Maria Paula Matos Marques

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Line ◽

Breast Cancer Cells ◽

Triple Negative ◽

Breast Adenocarcinoma ◽

Coumaric Acid ◽

Human Breast ◽

The Impact

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.

Download Full-text

Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions

Cells ◽

10.3390/cells10082044 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2044

Author(s):

Kamil Grubczak ◽

Anna Kretowska-Grunwald ◽

Dawid Groth ◽

Izabela Poplawska ◽

Andrzej Eljaszewicz ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Adenocarcinoma ◽

Ifn Gamma ◽

Checkpoint Proteins ◽

In Vitro Effects ◽

Blocking Antibodies ◽

Mcf 7

Drugs targeting immune checkpoint molecules have been found effective in melanoma, lung cancer, and other malignancies treatment. Recent studies on breast cancer demonstrated the significance of inhibitory anti-CTLA-4 and anti-PD-1 in the regulation of disease progression. However, seemingly the same types of breast cancer do not always respond unambiguously to immunotherapy. Thus, here we set out to analyze the in vitro effects of inhibiting CTLA-4 and PD-1 on interactions between co-cultured lymphocytes and two selected breast adenocarcinoma cell lines. Breast cancer cells were co-cultured with lymphocytes to evaluate the effects of CTLA-4 and PD-1 inhibition. Proliferation, cell cycle, and viability assessment were measured in cancer cells. IFN-gamma, IL-10, perforin, granzyme B production, and CTLA-4 and PD-1 expression were analyzed in lymphocytes. We found that administration of anti-CTLA-4 improved the anti-cancer activity of T cells with reduced proliferation and viability of MDA-MB-231. Lack of response was observed in the context of MCF-7. In addition, differential expression of checkpoint proteins was found between studied cancer cells lines. Inhibition of molecules was followed by IL-10 and IFN-gamma decrease in lymphocytes co-cultured with MDA-MB-231, not demonstrated in reference to MCF-7. Furthermore, CTLA-4 blockage was associated with reduction of CTLA-4+ and PD-1+ lymphocytes in MDA-MB-231, with a significant increase in MCF-7, reduced by anti-PD-1. Altogether, our study revealed that anti-CTLA-4 and anti-PD-1 treatment can improve lymphocytes effects on breast cancer cells. Favorable effects seemed to be related to breast cancer cells features as differential responses were reported. Novel blocking antibodies strategies should be tested for more effective cancer inhibition.

Download Full-text

Transition metal chelators, pro-chelators, and ionophores as small molecule cancer chemotherapeutic agents

Chemical Society Reviews ◽

10.1039/c9cs00373h ◽

2020 ◽

Vol 49 (12) ◽

pp. 3726-3747 ◽

Cited By ~ 5

Author(s):

Axel Steinbrueck ◽

Adam C. Sedgwick ◽

James T. Brewster ◽

Kai-Cheng Yan ◽

Ying Shang ◽

...

Keyword(s):

Transition Metal ◽

Cancer Cells ◽

Small Molecule ◽

Chemotherapeutic Agents ◽

Metal Chelators ◽

Iron Copper ◽

Copper And Zinc

Transition metal chelators and ionophores have shown promise as alternative chemotherapeutic strategies by selectively altering the concentrations of iron, copper, and zinc in cancer cells.

Download Full-text

Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells

Scientific Reports ◽

10.1038/s41598-021-84146-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Paulina Wigner ◽

Krzysztof Zielinski ◽

Magdalena Labieniec-Watala ◽

Agnieszka Marczak ◽

Marzena Szwed

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Mitochondrial Function ◽

Breast Cancer Cells ◽

Chemotherapeutic Agents ◽

Breast Adenocarcinoma ◽

Breast Cancer Cell Lines ◽

Antioxidant Systems ◽

Exact Nature ◽

Human Breast

AbstractDoxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX–Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX–Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX–Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX–Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.

Download Full-text

The Novel Method for Delivery miRNA-34a: a New Cationic PEGylated Niosomal Formulation for the Treatment of Breast Cancer

10.21203/rs.3.rs-650056/v1 ◽

2021 ◽

Author(s):

Najmeh Alsadat Abtahi ◽

Fateme Haghiralsadat ◽

Abolghasem Siyadatpanah ◽

Javad Zavar Reza ◽

Veeranoot Nissapatorn ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

High Efficiency ◽

Small Diameter ◽

Spherical Shape ◽

Cancer Drug ◽

Breast Adenocarcinoma ◽

Human Breast ◽

Mcf 7

Abstract Background: The reactive surface of nanoparticles makes it possible to simply modify with a biocompatible coating and load with therapeutic agents such as siRNA, miRNA, an anti-cancer drug, and antibody. MicroRNAs, like the noncoding RNAs, contribute critical to the regulation of numerous cellular functions via transcriptional silencing. MicroRNAs (miRNAs) have enormous potential in cancer treatment, however, it is difficult to deliver them effectively to most solid tumors. The encapsulation of miRNA-34a in niosome nanoparticles is an attractive strategy for biopharmaceutical resources against cancer. The present study investigated the effectiveness of anticancer activity against MCF-7 and T47D human breast adenocarcinoma cells of a new noiosome system composed of nonionic surfactants. Methods: We used the optimum formulations to transfer miRNA-34a to breast cancer cells, providing potential benefits, such as exceptionally high entrapment efficiency (almost 100%), spherical shape, suitable positive charge (zeta potential~ + 24 mV) and small diameter (~100 nm). Results: The miRNA-34a-niosomes represented improved cytotoxic activity against the cancer cells compared to readily dispersed miRNA-34a. The resulting data indicate that delivery of miRNA-34a via niosome can affect tumor suppression, highlighting its promising anticancer effects in breast cancer cells. Conclusion: In conclusion, the developed a new carrier to improve the delivery of miRNA-34a into the tumor cells. The formulation provided in the present work is stable with a sustained release, high efficiency of miRNA-34a loading having a diameter of 115 nm. miRNA loading is performed without potentially harmful chemical reactions. Niosomes loaded with miRNA-34a in this study represented significant cytotoxic effects against the human breast cancer MCF-7 and T47D cells, which highlights their potential effect on this type of cancer cells.

Download Full-text

Thrombospondin-1 (TSP-1) Stimulates Expression of Integrinα6 in Human Breast Carcinoma Cells: A Downstream Modulator of TSP-1-Induced Cellular Adhesion

Journal of Oncology ◽

10.1155/2010/645376 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Anitha S. John ◽

Vicki L. Rothman ◽

George P. Tuszynski

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Human Keratinocytes ◽

Cellular Adhesion ◽

Immunohistochemical Localization ◽

Breast Adenocarcinoma ◽

Human Breast ◽

Thrombospondin 1

Thrombospondin-1 (TSP-1) is involved in a variety of different cellular processes including cell adhesion, tumor progression, and angiogenesis. This paper reports the novel finding that TSP-1 upregulates integrinα6 subunit in human keratinocytes and human breast cancer cells resulting in increased cell adhesion and tumor cell invasion. The effect of TSP-1 onα6 subunit expression was examined in human keratinocytes and breast adenocarcinoma cell lines (MDA-MB-231) treated with TSP-1 and in TSP-1 stably transfected breast cancer cells. TSP-1 upregulatedα6 message and protein in these cells as revealed by differential display, Northern and Western blot analysis and immunohistochemical localization studies. The increased expression ofα6 was shown to mediate adhesion and invasion of these cells to laminin, a major component of the basement membrane and extracellular matrix (ECM). These data suggest that TSP-1 plays an integral role in the attachment of cells to the ECM facilitating cell motility and angiogenesis.

Download Full-text

FMSP-Nanoparticles Induced Cell Death on Human Breast Adenocarcinoma Cell Line (MCF-7 cells): Morphometric Analysis

10.20944/preprints201805.0204.v1 ◽

2018 ◽

Author(s):

Firdos Alam Khan ◽

Sultan Akhtar ◽

Sarah Ameen Almofty ◽

Dana Almohazey ◽

Munthar Alomari

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Breast Adenocarcinoma ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Surgical Interventions ◽

Mcf 7

Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, dose of 1.25µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5µg/mL and 50µg/mL respectively showed significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate FMSP-nanoparticles have ability to induce cell death in MCF-7 cells and may be considered as a potential anti-cancer agent for breast cancer treatments.

Download Full-text

Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells

Cancers ◽

10.3390/cancers13010136 ◽

2021 ◽

Vol 13 (1) ◽

pp. 136

Author(s):

Ching-Hsuan Liu ◽

Shu Hui Wong ◽

Chen-Jei Tai ◽

Cheng-Jeng Tai ◽

Yu-Chi Pan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Ursolic Acid ◽

Measles Virus ◽

Breast Cancer Cells ◽

Combined Treatment ◽

Oncolytic Viruses ◽

Drug Dissolution ◽

Breast Adenocarcinoma ◽

Autophagic Flux

Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women’s cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA’s potentiation of apoptotic killing by MV. To circumvent UA’s poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA’s applicability.

Download Full-text