Agent For Treatment Of Breast Cancer Research Articles

Lactic Acid Bacteria-Derived Postbiotics as Adjunctive Agents in Breast Cancer Treatment to Boost the Antineoplastic Effect of a Conventional Therapeutic Comprising Tamoxifen and a New Drug Candidate: An Aziridine–Hydrazide Hydrazone Derivative

Breast cancer is associated with high mortality and morbidity rates. As about 20–30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine–hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics’ potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.

THE APPLICATION OF BIOANALYTICAL METHOD OF TAMOXIFEN AND ITS ACTIVE METABOLITES FOR THERAPEUTIC DRUG MONITORING IN BREAST CANCER PATIENTS: A REVIEW

Breast cancer is the most common cancer around the world and in Indonesia. The most widely used agent for breast cancer treatment is tamoxifen, with a fixed dose of 20 mg per day. Tamoxifen is metabolized by cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) to endoxifen and 4-hydroxytamoxifen, which have 30-to 100-fold more potent antiestrogenic activity than tamoxifen. High variations of CYP3A4 and CYP2D6 genes can lead to interpatient variability in its metabolites concentration. The dose can be increased to 40 or 60 mg per day based on individual needs. Therapeutic drug monitoring (TDM) is required to measure the concentration of tamoxifen and its metabolites to decide the individualized dose. The measurement of drug levels should use a sensitive, selective, accurate, precise, and reliable bioanalytical method. Various bioanalytical methods have been developed in several matrices: urine, scalp hair, serum, plasma, dried blood spot (DBS), and volumetric absorptive microsampling (VAMS) samples, with different sample preparations, and frequently using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The bioanalytical method of tamoxifen and its metabolites in the DBS sample was more suitable in the TDM application due to the low invasive sampling technique, more stable sample, and rapid sample preparation. Therefore, it is more time-and cost-efficient than the other methods.

Metabolic Profiling, in vitro Cytotoxicity and in silico Investigation of Lycium shawii Roem. Extract

Background: Breast cancer is a prevalent global health concern. Traditional medicine often incorporates the use of medicinal plants to address various diseases. Methods: The cytotoxicity, oxidative stress and cell migration effects of saponin and phenol extracts were evaluated through MTT assay, ROS analysis and wound-healing assay. Following the identification of the active extract, it underwent GC-MS analysis and in silico investigations. Result: Our results revealed significant inhibition of cell proliferation in MDA-MB-231 (IC50:407.3 μg/mL) and HUVECs (IC50:500 μg/mL), which was achieved only with the ethyl acetate extract (Fraction 2). Fraction 2 extract induced notable morphological changes and significantly inhibited time-dependent migration in MDA-MB-231 cells. Additionally, it elevated cellular ROS levels compared to the control cells. In molecular docking analysis, out of the 51 chosen secondary metabolites from L. shawii, stigmast-5-en-3-ol, (3α,24S) (-10.0 kcal/mol) and lup-20(29)-ene-3,28-diol (-9.5 kcal/mol) were found to be the best docked to their respective targets-6CHZ and 4MAN, respectively. Therefore, this plant holds promise as a potential therapeutic agent for breast cancer treatment.

Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results.

Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.

Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6

PurposeThis study will focus on 4T1 cells, a murine mammary adenocarcinoma cell line, as the primary research subject. We aim to investigate the inhibitory effects and mechanisms of propranolol on epithelial–mesenchymal transition (EMT) in breast cancer cells, aiming to elucidate this phenomenon at the miRNA level.MethodsIn this study, the EMT inhibitory effect of propranolol was observed through in vitro and animal experiments. For the screening of potential target miRNAs and downstream target genes, second-generation sequencing (SGS) and bioinformatics analysis were conducted. Following the screening process, the identified target miRNAs and their respective target genes were confirmed using various experimental methods. To confirm the target miRNAs and target genes, Western Blot (WB), reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence experiments were performed.ResultsIn this study, we found that propranolol significantly reduced lung metastasis in 4T1 murine breast cancer cells (p < 0.05). In vitro and in vivo experiments demonstrated that propranolol inhibited the epithelial–mesenchymal transition (EMT) as evidenced by Western Blot analysis (p < 0.05). Through next-generation sequencing (SGS), subsequent bioinformatics analysis, and PCR validation, we identified a marked downregulation of miR-499-5p (p < 0.05), suggesting its potential involvement in mediating the suppressive effects of propranolol on EMT. Overexpression of miR-499-5p promoted EMT, migration, and invasion of 4T1 cells, and these effects were not reversed or attenuated by propranolol (Validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). Sox6 was identified as a functional target of miR-499-5p, with its downregulation correlating with the observed EMT changes (p < 0.05). Silencing Sox6 or overexpressing miR-499-5p inhibited Sox6 expression, further promoting the processes of EMT, invasion, and migration in 4T1 cells. Notably, these effects were not alleviated by propranolol (validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). The direct interaction between miR-499-5p and Sox6 mRNA was confirmed by dual-luciferase reporter gene assay.ConclusionThese results suggest that propranolol may have potential as a therapeutic agent for breast cancer treatment by targeting EMT and its regulatory mechanisms.

Potential of natural flavonoids to target breast cancer angiogenesis (review).

Angiogenesis is the process by which new blood vessels form and is required for tumour growth and metastasis. It helps in supplying oxygen and nutrients to tumour cells and plays a crucial role in the local progression and distant metastasis of, and development of treatment resistance in, breast cancer. Tumour angiogenesis is currently regarded as a critical therapeutic target; however, anti-angiogenic therapy for breast cancer fails to produce satisfactory results, owing to issues such as inconsistent efficacy and significant adverse reactions. As a result, new anti-angiogenic drugs are urgently needed. Flavonoids, a class of natural compounds found in many foods, are inexpensive, widely available, and exhibit a broad range of biological activities, low toxicity, and favourable safety profiles. Several studies find that various flavonoids inhibit angiogenesis in breast cancer, indicating great therapeutic potential. In this review, we summarize the role of angiogenesis in breast cancer and the potential of natural flavonoids as anti-angiogenic agents for breast cancer treatment. We discuss the value and significance of nanotechnology for improving flavonoid absorption and utilization and anti-angiogenic effects, as well as the challenges of using natural flavonoids as drugs.

Apigenin promotes apoptosis of 4T1 cells through PI3K/AKT/Nrf2 pathway and improves tumor immune microenvironment in vivo.

The 2022 US Cancer Statistics show that breast cancer is one of the most common cancers in women. Epidemiology has shown that adding flavonoids to the diet inhibits cancers that arise in particular women, such as cervical cancer, ovarian cancer, and breast cancer. Although there have been research reports on apigenin (API) and breast cancer, its anti-tumor effect and potential mechanism on breast cancer have not yet been clarified. Therefore, in this study, we used 4T1 cells and a 4T1 xenograft tumor mouse model to investigate the antitumor effect of API on breast cancer and its underlying mechanism. In vitro, we used MTT, transwell, staining, and western blotting to investigate the inhibitory effect of apigenin on 4T1 and the underlying molecular mechanism. In vivo by establishing a xenograft tumor model, using immunohistochemistry, and flow cytometry to study the inhibitory effect of apigenin on solid breast tumors and its effect on the tumor immune microenvironment. The results showed that API can induce breast cancer cell apoptosis through the PI3K/AKT/Nrf2 pathway and can improve the tumor immune microenvironment in mice with breast tumors, thereby inhibiting the growth of breast cancer. Thus, API may be a promising agent for breast cancer treatment.

Nicotinamide Loaded Chitosan Nanocomplex Shows Improved Anticancer Potential: Molecular Docking, Synthesis, Characterization and In vitro Evaluations

Abstract: This study aimed to prepare and characterize chitosan nanoparticles encapsulating a nicotinamide derivative (Ni-CS-NP). Additionally, the therapeutic effectiveness, cytotoxicity, selectivity, and immunomodulatory properties of Ni-CS-NP were evaluated in human breast and colon cancer cell lines. Chitosan nanoparticles have shown potential as drug delivery carriers due to their biocompatibility and controlled release properties. Encapsulating a nicotinamide derivative further enhances the therapeutic potential of these nanoparticles. Computational studies were employed to validate the binding interactions, providing crucial insights into the formulation's stability and effectiveness. The primary objective was to assess the cytotoxicity and safety profiles of Ni-CS-NP in human cancer cell lines. Moreover, this study aimed to investigate the specific mechanisms underlying its cytotoxic effects, including its impact on cell cycle progression, apoptosis induction, and immunomodulation. Ni-CS-NP were synthesized using the ionic gelation method and characterized using Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermo gravimetric analysis. The cytotoxicity was evaluated in breast and colon cancer cell lines through the MTT assay. Selectivity indices were calculated to determine the safety profiles. The inhibition of VEGFR-2, induction of apoptosis, cell cycle disruption, and immunomodulatory effects were assessed through molecular assays. Computational analysis demonstrated favorable binding interactions through the Ni-CS-NP complex. The characterization studies confirmed the successful synthesis of Ni-CS-NP with well-defined structural and thermal properties. Ni-CS-NP exhibited remarkable cytotoxicity with a superior safety profile against MCF7 and HCT 116 cell lines showing IC50 values of 2.32 and 2.70 μM, respectively, surpassing sorafenib's efficacy (IC50 = 4.12 and 7.55 μM, respectively). Additionally, Ni-CS-NP effectively inhibited VEGFR-2, induced both early and late apoptosis, and disrupted the cell cycle progression in MCF7 cells. Notably, Ni-CS-NP demonstrated significant immunomodulatory effects by reducing TNF-α and IL-2 levels compared to dexamethasone. The encapsulation of a nicotinamide derivative within chitosan nanoparticles (Ni-CS-NP) through the ionic gelation method proved successful. Ni-CS-NP displayed potent cytotoxicity, superior safety profiles, and promising immunomodulatory effects in human breast cancer cells. These findings highlight the potential of Ni-CS-NP as a novel therapeutic agent for breast cancer treatment, warranting further investigation for clinical applications.

Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells.

Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant "Myrmecia pilosula", as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3's cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (p < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results.

Synthesis of new imine-/amine-bearing imidazo[1,2-a]pyrimidine derivatives and screening of their cytotoxic activity.

Imidazo[1,2-a]pyrimidine derivatives bearing imine groups (3a-e) were successfully synthesized in moderate to good yields using microwave-assisted heating. Corresponding amine derivatives (4a-e) were also obtained by the reduction reaction of the imine derivatives (3a-e). All synthesized products were characterized by FT-IR, 1H NMR, 13C NMR, and LC-MS spectroscopic techniques. In silico ADMET, Lipinski, and drug-likeness studies of the compounds were conducted and all were found to be suitable drug candidates. The cytotoxicity of the potential drug molecules was screened against the breast cancer cell lines MCF-7 and MDA-MB-231 and the healthy model HUVEC by the sulforhodamine B method. According to the antiproliferative studies, compounds 3d and 4d showed remarkable inhibition of MCF-7 cells with IC50 values of 43.4 and 39.0 μM and of MDA-MB-231 cells with IC50 values of 35.9 and 35.1 μM, respectively. In particular, compound 3d selectively inhibited the proliferation of MCF-7 1.6-fold and MDA-MB-231 2.0-fold relative to healthy cells. Moreover, the apoptotic mechanism studies indicated that compound 4d induced apoptosis by moderately increasing the ratio of Bax/Bcl-2 genes. Imidazo[1,2-a]pyrimidine derivative 3d, a promising cytotoxic agent, may be helpful in the discovery of new and more efficient anticancer agents for breast cancer treatment.

Trends in research of exosomes associated with breast cancer over the past decade: a scientometric analysis.

Breast cancer remains a significant global health challenge, accounting for 2.3 million new cases in 2020 and ranking as the most prevalent cancer by incidence and the fourth in cancer-related mortality worldwide. In China, breast cancer also rapidly increases incidence and burden. The research of exosomes in breast cancer has attracted more and more attention and has a rapid development. Recognizing the pivotal role of exosomes in breast cancer research, we have undertaken a comprehensive scientometric analysis of pertinent scholarly articles published over the past decade to elucidate the current research landscape for researchers. In this study, we gathered all pertinent publications from the Web of Science. Biblioshiny (a web interface for Bibliometrix), VOSviewer software, and CiteSpace software were used to analyze the information on publications, including global trends, countries, institutions, journals, authors, keywords, and citations. A total of 1,239 articles and 625 review articles were retrieved. The annual global publication output has an increased trend in recent decades overall. China contributed the most articles. The publications of the USA had the most total link strength. Nanjing Medical University had the most total link strength. The most relevant source was the International Journal of Molecular Sciences. Tang JH contributed the most articles and had the highest H-index, G-index, and total link strength. The most cited document was "Tumor exosome integrins determine organotropic metastasis", with 2730 citations. The basic themes included "exosomes", "expression", "cells", "identification", "biomarkers", and "serum". The keyword "membrane vesicle" had the strongest bursts. The keywords "target", "biology", "suppressor cell", "molecular mechanism", "tumor progression", "inhibitor", and "model" appeared as prominent focal points in current research and active areas of exploration. Over the past decade, exosome research in breast cancer has undergone a discernible evolution, shifting from broader investigations of exosome roles to focused exploration of specific pathways relevant to breast cancer. Notably, the emphasis has extended to the clinical application of exosomes as biomarkers and potential therapeutic agents in breast cancer treatment.

Propolis nanoparticles synthesis and characterization with cytotoxic and apoptotic effects on breast cancer cells

The aim of this work was to investigate the antiproliferative and pro-apoptotic effects of propolis on human breast cancer cells using a simple and inexpensive nanoformulation. Various methods were used to characterize the surface and morphology of propolis nanoparticles (NP-Pro), including UV-VIS, FTIR, DLS, and EDX-SEM. The cytotoxic activity of MCF-7, MDA-MB-231 breast cancer cells was measured by XTT technique and compared with healthy cells (MCF-10A). The apoptotic effect of NP-Pro was assessed by flow cytometry using Annexin/PI. The IC50 values of NP-Pro on MCF-7, MDA-MB-231 and MCF-10A cells were 13.67 ± 0.89, 17.89 ± 0.6, 29.9 ± 0.56 µg, respectively. According to these findings, the NP-Pro form we prepared was more cytotoxic on cancer cells than propolis. Cancer cells had much stronger apoptotic activity than healthy cells (p < 0.0001). In this work, NP-Pro was produced through a distinct, straightforward, and low-cost method. In summary, the NP-Pro we synthesized may be a promising potential agent for breast cancer treatment due to its specific cytotoxicity via apoptosis.

Effect of curcumin on lipid profile, fibrosis, and apoptosis in liver tissue in abemaciclib-administered rats

Abemaciclib (ABEM) is an important antitumor agent for breast cancer treatment. However, the side-effects of ABEM are unclear in the liver. This study investigated the protective effect of curcumin (CURC) on liver damage caused by ABEM. The rats were divided into five groups with eight animals in each group; Control, DMSO (150 µL for per rats), CURC, 30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CURC (26 mg/kg/day ABE, 30 mg/kg/day) groups. Injections were administered daily for 28 days. The levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and hepatic tissue fibrosis, caspase-3, Bax, and TNF-α expression were higher in the ABE group compared to the control group (p < 0.05). Also, these parameters in the ABEM + CURC group were lower than in the ABE group (p < 0.05). The results showed that ABE administration could cause liver damage and increase fibrosis in the liver. In addition, it was shown that co-administration of CURC with ABE could suppress the levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and fibrosis, caspase-3, Bax, and TNF-α expressions in the liver. These data are the first in the literature. Therefore, the administration of CURC following ABE may be a therapeutic agent in preventing liver damage.

A Concise Review on Natural Products and Their Derivatives for Breast Cancer Treatment.

Cancer is a leading cause of death worldwide. Among other cancers, breast cancer has been found to produce maximum number of cases in 2020. Different factors including geographical, genetic, hormonal, oral contraceptives and modern lifestyle could be responsible for the development of breast cancer and different pathways can be targeted for breast cancer treatment. The various conventional approaches used for the treatment of breast cancer including radiotherapy, chemotherapy, hormone and immunotherapy. But due to the side effects associated with these conventional treatments such as non-selectivity, multidrug resistance and bioavailability, there is a need for the development of better therapeutic agents for breast cancer treatment. Several natural products have been explored for breast cancer treatment. However, many of these natural products suffered from the limitations of poor water solubility and possess toxic side effects. To overcome these limitations, several structural analogs of natural products have been synthesized and possess potent anti-breast cancer effects with less side effects over their precursor molecules. In the present manuscript, we describe the pathogenesis of breast cancer, some potent natural products used in the treatment of breast cancer and their selected structural analogs possessing potent anti-breast cancer effects. Database such as Science direct, Pubmed and Google scholar were searched using keywords 'risk factors', 'screening methods','receptors', and 'natural products and derivatives', Registered clinical trials on selected natural products were also analyzed. Present study concludes that eight selected natural products and their derivatives possess wide potential to exhibit anti-breast cancer effects and could be explored further to develop better chemotherapeutic agents against breast cancer.

Sertraline as a potential cancer therapeutic approach: Biological relevance of TCTP in breast cancer cell lines and tumors

PurposeThis study aimed to evaluate the role of Translationally Controlled Tumor Protein (TCTP) in breast cancer (BC) and investigate the effects of sertraline, a serotonin selective reuptake inhibitor (SSRI), on BC cells. The objective was to assess the potential of sertraline as a therapeutic agent in BC treatment by examining its ability to inhibit TCTP expression and exert antitumor effects. Material and MethodsWe utilized five different BC cell lines representing the molecular heterogeneity and distinct subtypes of BC, including luminal, normal-like, HER2-positive, and triple-negative BC. These subtypes play a crucial role in determining clinical treatment strategies and prognosis. ResultsThe highest levels of TCTP were observed in triple-negative BC cell lines, known for their aggressive behavior. Sertraline treatment reduced TCTP expression in BC cell lines, significantly impacting cell viability, clonogenicity, and migration. Additionally, sertraline sensitized triple-negative BC cell lines to cytotoxic chemotherapeutic drugs (doxorubicin and cisplatin) suggesting its potential as an adjunctive therapy to enhance the chemotherapeutic response. Bioinformatic analysis of TCTP mRNA levels in TCGA BC data revealed a negative correlation between TCTP levels and patient survival, as well as between TCTP/tpt1 and Ki67. These findings contradict our data and previous studies indicating a correlation between TCTP protein levels and aggressiveness and poor prognosis in BC. ConclusionsSertraline shows a promise as a potential therapeutic option for BC, particularly in triple-negative BC. Its ability to inhibit TCTP expression, enhance chemotherapeutic response, highlights its potential clinical utility in BC treatment, specifically in triple-negative BC subtype.

Induction of Unfolded Protein Response by Tannic Acid Triggers Apoptosis in MDA-MB-231 Breast Cancer Cells.

Endoplasmic reticulum (ER) stress can reduce cell survival and enhances the apoptosis of cancer cells. Plant polyphenols like tannic acid trigger ER stress and apoptosis and therefore can be a novel agent for the treatment of cancer. In this study, we investigated the effect of tannic acid on survival, migration, colony formation, ER stress pathway, and apoptosis of the MDA-MB-231 breast cancer cells. The MTT assay was performed to investigate the effect of tannic acid on the cell survival of breast cancer cells. We used the qPCR method to reveal the effect of tannic acid on the Bak, CHOP, ATF4, P21, MMP-2, and Bcl-2 expression. Also, colony formation, cell migration, and Hoechst staining assays were employed. The results of the MTT test showed that tannic acid reduced the cell survival rate. In the qPCR assay, we found that tannic acid decreased the expression levels of MMP-2, Bcl-2, ATF4, and CHOP genes, paradoxically, enhanced the expression of Bak and P21 genes. The colony formation and cell migration assays indicated that tannic acid significantly diminished breast cancer cell proliferation and migration, respectively. In the apoptosis assay, tannic acid increased the number of apoptotic cells. Tannic acid increases the rate of cell death but decreases viability and cell migration. Moreover, tannic acid induces apoptosis in breast cancer cells. Overall, our study demonstrates that tannic acid induces ER stress by increasing the genes which are playing role in ER stress pathway. These results show that tannic acid can be used as an effective agent for breast cancer treatment.

β-Carboline-α-aminophosphonate Derivative: A Promising Antitumor Agent for Breast Cancer Treatment.

Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-β-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester (BCP-1) in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). BCP-1 has an α-aminophosphonate unit linked to the β-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of BCP-1 was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that BCP-1 inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and caspases, as well as a decrease in the anti-apoptotic protein Bcl-2, indicated potential induction of apoptosis in the MDA-MB-231 cells. While in MCF-7 cells, BCP-1 activated the autophagic death pathway, which was demonstrated by an increase in autophagic vacuoles and acidic organelles, in addition to increased expression of LC3I/LC3II and reduced SQSTM1/p62 expression. Further, BCP-1 demonstrated antimetastatic potential by reducing MMP-9 expression and cell migration in both breast cancer cell lines. In conclusion, BCP-1 is a promising candidate for breast cancer chemotherapy.

Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo

Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of β-catenin (β-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of β-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit β-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.

Effect of evernic acid on human breast cancer MCF-7 and MDA-MB-453 cell lines via thioredoxin reductase 1: A molecular approach.

Thioredoxin reductase 1 (TrxR1) has emerged as an important target for anticancer drug development due to its overexpression in many human tumors including breast cancer. Due to the serious side effects of currently used commercial anticancer drugs, new natural compounds with very few side effects and high efficacy are of great importance in cancer treatment. Lichen secondary metabolites, known as natural compounds, have diverse biological properties, including antioxidant and anticancer activities. Herein, we aimed to determine the potential antiproliferative, antimigratory, and apoptotic effects of evernic acid, a lichen secondary metabolite, on breast cancer MCF-7 and MDA-MB-453 cell lines and afterward to investigate whether its anticancer effect is exerted by TrxR1-targeting. The cytotoxicity results indicated that evernic acid suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose-dependent manner and the IC50 values were calculated as 33.79 and 121.40 μg/mL, respectively. Migration assay results revealed the notable antimigratory ability of evernic acid against both cell types. The expression of apoptotic markers Bcl2 associated X, apoptosis regulator, Bcl2 apoptosis regulator, and tumor protein p53 by quantitative real-time polymerase chain reaction and western blot analysis showed that evernic acid did not induce apoptosis in both cell lines, consistent with flow cytometry results. Evernic acid showed its anticancer effect via inhibiting TrxR1 enzyme activity rather than mRNA and protein expression levels in both cell lines. In conclusion, these findings suggest that evernic acid has the potential to be evaluated as a therapeutic agent in breast cancer treatment.

Nano Transdermal Delivery Potential of Fucoidan from Sargassum sp. (Brown Algae) as Chemoprevention Agent for Breast Cancer Treatment

Conventional chemotherapy substances are associated with mild to severe side effects that affect both healthy and cancer cells. It is presumed to improve therapeutic efficacy in coexistence reducing chemotherapy’s side effects. Fucoidan is an anticancer bioactive compound derived from Sargassum sp. that has low cytotoxic activity. The purpose of this study was to explore the effectiveness of anticancer activities of fucoidan from Sargassum sp. against breast cancer then analyze the suitability of nano transdermal patch of fucoidan and blueprint the long-term research design of nano transdermal patch as a chemoprevention agent in the chemotherapeutic management of breast cancer. This research was performed through a literature study and in silico study by imposing carbonic anhydrase IX (CA IX) as a marker of hypoxia and metastatic state of cancer cells. The results showed that the fucoidan from Sargassum sp. effectively induced apoptosis and prevented metastasis of breast cancer cells through the Bcl-2, Bcl-w, and bad pathways. Fucoidan, in addition, was predicted to inhibit CA IX by Glu4 Glu5, Leu7, Pro8, and Asp6 residues. Therefore, the delivery of fucoidan is favored to have a local effect on the site of breast cancer cells by nano transdermal patch preparations using fucoidan nanoparticle polymer. Further nano transdermal patch development as a treatment for breast cancer is suggested through the stages of formulation optimization, optimum formula activity testing, patent filing, and distribution in health services.