Anti-breast Cancer Drug Research Articles

A novel approach to breast cancer Assessing the promise of RF16662 on MCF-7 breast cancer cells

Abstract. Breast cancer, a prevalent global health issue, often poses challenges due to resistance apoptosis. This study explores the potential of RF16662, a derivative of naphthyridine, as a novel compound for breast cancer treatment. Naphthyridine compounds, known for inducing necroptosis in cancer cells, offer a unique avenue for addressing apoptosis-resistant cancers. RF16662s efficacy was evaluated through three experiments on MCF-7 breast cancer cells. The MTT cell viability assay demonstrated a strong negative correlation between RF16662 concentration and cell viability, indicating its effectiveness in inhibiting MCF-7 cellular activity. DNA fragmentation analysis revealed substantial DNA fragmentation in cells treated with RF16662, suggesting necroptosis induction. MLKL immunofluorescence confirmed the significant difference in relative MLKL expression between untreated and treated cells, further supporting the induction of necroptosis. This study provides robust evidence of RF16662s efficacy against MCF-7 breast cancer cells. However, variations in MLKL immunofluorescence data suggest the need for repeated experiments to minimize the standard deviation. The results highlight RF16662s potential as an anti-breast cancer drug, offering a promising avenue for future research and potential therapeutic development. While its efficacy against other cancer types remains unknown, RF16662 emerges as a noteworthy candidate in the ongoing quest for innovative breast cancer treatments.

Strategies to Improved Breast Cancer Treatment Associated With Cardiotoxicity

Abstract. In recent years, breast cancer has developed rapidly. Many women suffer from breast cancer, making the study of its treatment extremely important. The drugs used in breast cancer therapy have shown beneficial effects, but some cause cardiotoxic side effects wich deserve close attention. Cardiotoxicity includes a range of effects, such as arrythmia, cardiac dyfunction and even heart failure, which could be a threaten to life health. Therefore, it is crucial and necessary to deal with the cardiotixicity side effect during breast cancer therapy. Doing so will provide patients better options for their treatment. Three drugs have been proven to have cardiotoxic effects, including anthracyclines(eg:Doxorubicin), HER-2-targeting drug(Tratzutmab), and Cyclophosphamide. Although numerous studies have extensively researched how to mitigate the cardiotoxic effects of anti-breast cancer drugs, few articles have summarized and discussed these findings. This current situation results in a lack of comprehensive treatment plans in clinical practice. Therefore, this paper aims to review these studies and discuss the main drugs used to reduce the toxicity of three commonly used antineoplastic agents, in the hope of providing more comprehensive guidance for clinical medication.

Synthesis and Evaluation of 3,5-Disubstituted-1,2,4-Oxadiazolyl Benzamides as Potential Anti-Breast Cancer Agents: In Vitro and In Silico Studies.

Herein, the synthesis, anti-cancer evaluation, and in silico studies of a series of 1,2,4-oxadiazole compounds (8-15) are disclosed. The synthesized molecules were tested in vitro for anti-cancer activity against MCF-7, MDA-MB-231, HeLa, Ishikawa cell lines and human embryonic kidney (HEK-293) cell lines. Among the synthesized compounds, 9 and 15 exhibited significant cytotoxicity, with IC50 values of 7.82 μM and 6.02 μM, respectively, against MCF-7 cell line, better than that of anti-breast cancer drug, tamoxifen (IC50 = 11.92 μM), used as control. Significantly, both 9 and 15 exhibited very low toxicity (IC50 > 20 µM) against normal HEK-293 cells. This suggests them as potentially effective anti-cancer lead molecules. The in vitro anti-cancer data was supported by in silico studies which also identified compounds 9 and 15 as potent inhibitors of the 17β-hydroxysteroid dehydrogenase1 (17β-HSD1) proteins, demonstrating strong interactions and stability The atom-based QSAR model exhibited high accuracy, significant regression, and predictive reliability, aiding in understanding and optimizing biological activity. The drug-likeness study of compounds 9 and 15 indicated favorable pharmacokinetics, with in silico toxicity predictions showing compound 15 to be non-toxic. These findings suggest compounds 9 and 15 as potential lead molecules against breast cancer.

Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv. inhibits the function and catalysis of human 17β-hydroxysteroid dehydrogenase 1

Cancer is a leading cause of global death. Medicinal plants have gained increasing attention in cancer drug discovery. In this study, the stem bark extract of Olax subscorpioidea, which is used in ethnomedicine to treat cancer, was subjected to phytochemical investigation leading to the isolation of oleanolic acid (OA). The structure was elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic (NMR) data, and by comparing its data with previously reported data. Molecular docking was used to investigate the interactions of OA with nine selected cancer-related protein targets. OA docked well with human 17β-hydroxysteroid dehydrogenase type-1 (17βHSD1), caspase-3, and epidermal growth factor receptor tyrosine kinase (binding affinities: −9.8, −9.3, and −9.1 kcal/mol, respectively). OA is a triterpenoid compound with structural similarity to steroids. This similarity with the substrates of 17βHSD1 gives the inhibitor candidate an excellent opportunity to bind to 17βHSD1. The structural and functional dynamics of OA-17βHSD1 were investigated by molecular dynamics simulations at 240 ns. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (–52.76, and −63.56 kcal/mol, respectively). The average C-α root mean square of deviation (RMSD) value of OA (1.69 Å) compared with the unbound protein (2.01 Å) indicated its high stability at the protein’s active site. The binding energy and stability at the active site of 17βHSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.

Revealing the molecular mechanism of baohuoside I for the treatment of breast cancer based on network pharmacology and molecular docking

Ethnopharmacological relevanceIn Traditional Chinese Medicine (TCM), there are many prescriptions for treating breast cancer (BC) that utilize the herb Epimedium brevicornum Maxim, which warms and replenishes kidney yang. Baohuoside I (BI) is a flavonoid compound found in Epimedium brevicornum Maxim. As a single glycoside, it is not easily hydrolyzed in the intestine and is typically absorbed as a precursor. As a natural product with potential anti-cancer properties, studies have shown that BI possesses anti-cancer activity and can inhibit the invasion and migration of BC cells. However, its underlying mechanisms remain unclear, thus further research is needed to validate its modern mechanisms for traditional uses. Aim of the studyThis study aimed to explore the regulatory mechanism of BI in the signaling pathways of BC cells through network pharmacology (NP), molecular docking (MD) techniques and cellular experiments. MethodsPotential targets were predicted using public databases, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Key signaling pathways were validated through MD techniques, cellular experiments, RNA interference and Western blot (WB) analysis. ResultsTreatment-associated targets included SRC, MAPK1, HSP90AA1, PIK3CA, TP53, AKT1, and EGFR. GO enrichment, KEGG enrichment analyses, and MD results indicated that BI exerts its anti-breast cancer effects by inhibiting the tyrosine kinase activity of EGFR, as well as through downstream MAPK signaling pathway and PI3K-Akt signaling pathway pathways. In vitro experiments confirmed that BI primarily induce cell apoptosis through the EGFR-mediated MAPK signaling pathway and PI3K-Akt signaling pathway. ConclusionBI can inhibit EGFR activation and promote BC cell apoptosis through the MAPK signaling pathway and PI3K-Akt signaling pathway, thereby exerting therapeutic effects on BC. This study not only provides experimental evidence for the accuracy of NP but also offers an effective approach for rational utilization of Baohuoside I-like flavonoid compounds as anti-breast cancer drugs.

Retraction Note: Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate

Retraction Note: Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate

A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations.

Metastasis of breast cancer is the main cause of death for patients with breast cancer. The interaction between metadherin (MTDH) and staphylococcal nuclease domain 1 (SND1) plays a pivotal role in promoting breast cancer development. However, the binding details between MTDH and SND1 remain unclear. In this study, we employed all-atom molecular dynamics simulations (MDs) and conducted binding energy calculations to investigate the binding details and the impact of key residue mutations on binding. The mutations in key residues have not significantly affected the overall stability of the structure and the fluctuation of residues near the binding site; they have exerted a substantial impact on the binding of SND1 and MTDH peptide. The electrostatic interactions and van der Waals interactions play an important role in the binding of SND1 and the MTDH peptide. The mutations in the key residues have a significant impact on electrostatic and van der Waals interactions, resulting in weakened binding. The energy contributions of key residues mainly come from the electrostatic energy and van der Waals interactions of the side chain. In addition, the key residues form an intricate and stable network of hydrogen bonds and salt-bridge interactions with the MTDH peptide. The mutations in key residues have directly disrupt the interactions formed between SND1 and MTDH peptide, consequently leading to changes in the binding mode of the MTDH peptide. These analyses unveil the detailed atomic-level interaction mechanism between SND1 and the MTDH peptide, providing a molecular foundation for the development of antibreast cancer drugs.

Repositioning fluphenazine as a cuproptosis-dependent anti-breast cancer drug candidate based on TCGA database

Breast cancer is one of the most prevalent malignancies among women. Enhancing the prognosis is an effective approach to enhance the survival rate of breast cancer. Cuproptosis, a copper-dependent programmed cell death process, has been associated with patient prognosis. Inducing cuproptosis is a promising approach for therapy. However, there is currently no anti-breast cancer drug that induces cuproptosis. In this study, we repositioned the clinical drug fluphenazine as a potential agent for breast cancer treatment by inducing cuproptosis. Firstly, we utilized the Cancer Genome Atlas (TCGA) database and Connectivity Map (CMap) database to identify 22 potential compounds with anti-breast cancer activity through inducing cuproptosis. Subsequently, our findings demonstrated that fluphenazine effectively suppressed the viability of MCF-7 cells. Fluphenazine also significantly inhibited the viability of triple negative breast cancer cells MDA-MB-453 and MDA-MB-231. Furthermore, our study revealed that fluphenazine significantly down-regulated the expression of potential prognostic biomarkers associated with cuproptosis, increased copper ion levels, and reduced intracellular pyruvate accumulation. Additionally, it up-regulated the expression of FDX1 at both the mRNA and protein levels, which has been reported to play a crucial role in the induction of cuproptosis. These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Optimized Modeling of Anti-Breast Cancer Drug Candidates

Optimized Modeling of Anti-Breast Cancer Drug Candidates

Novel pyrrole-chromone based chalcones: Synthesis and their anti-breast cancer activity: An in-silico study

Newer Pyrrole-Chromones Chalcones (I–VII) were prepared by a simple method. among the series of compounds, compound −1 which was synthesized with 30 % of NaOH solution, at temperature of 60–65 °C with twelve hours of reaction time resulted in good yield. While, the other compounds under same and varying conditions resulted in less yield. Existing reports showed that this group of compounds showed insulysin inhibition, interleukin antagonist, and membrane integrity agonist activities. The proteins EGFR and HER-2 which are over expressed in breast cancer, in In silico studies with the titled compounds showed strong binding affinity when compared to the standard drug tamoxifen, which clearly indicate that these compounds possess anti-breast cancer activity. Hence, it can be concluded that these compounds has the potential to develop as anti-breast cancer drugs.

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure-activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

Investigating the potent TOPO IIα inhibitors in breast cancer through the study of computational drug discovery research approaches.

Breast cancer (BC) is the second-leading cause of cancer after lung cancer. The disease has affected millions of people and resulted in many deaths. In the metastasis of breast cancer cells, Topoisomerase IIα plays a vital role. Therefore, this investigation aims to identify potential flavonoid compounds against BC by inhibiting this enzyme at an early stage. Based on previous studies, we selected and screened several plant-derived flavonoid compounds with potential anti-breast cancer activity using PyRx 0.8 and Schrodinger applications for preliminary molecular docking: the highest docking scores of Myricetin (-11.6kcal/mol) and Quercetin (-10.0kcal/mol). Next, we evaluated the top four compounds on the Way2Drug server to complete the cytotoxicity evaluation, which demonstrated anti-cancer and anti-breast cancer activity in various cell lines. According to pharmacokinetics studies, four compounds exhibited outstanding values and functioned similar to drug-like molecules. Moreover, Myricetin, Quercetin, and Morin displayed the highest number of hydrogen bonds, with the corresponding receptor forming residues asn120, thr147, and lys168. The protein-ligand complexes were validated using the Desmond simulator, and their data were compared to the anti-breast cancer drug Doxorubicin. In the simulation analysis, various parameters were evaluated, including RMSD, RMSF, Rg, SASA, MolSA, PSA, and hydrogen bond interaction. Finally, validated our dynamic simulation result with MM-GBSA operation, and Myricetin and Quercetin had the greatest score of -72.74344651, -66.66771823kcal/mol, which is outstanding than the control drug. Hence, the computational research approach determined that Myricetin, Quercetin, and Morin could be industrially developed for the alternative treatment of breast cancer following additional confirmation from animal and cell line studies.

Discovery of acetophenone/piperazin-2-one hybrids as selective anti-TNBC cancer agents by causing DNA damage

Twenty-five acetophenone/piperazin-2-one (APPA) hybrids were designed and synthesized based on key pharmacophores found in anti-breast cancer drugs Neratinib, Palbociclib, and Olaparib. Compound 1j exhibited good in vitro antiproliferative activity (IC50 = 6.50 μM) and high selectivity (SI = 9.2 vs HER2-positive breast cancer cells SKBr3; SI = 7.3 vs normal breast cells MCF-10A) against triple negative breast cancer (TNBC) cells MDA-MB-468. In addition, 1j could selectively cause DNA damage, inducing the accumulation of γH2AX and P53 in MDA-MB-468 cells. It also reduced the phosphorylation level of P38 and the expression of HSP70, which further prevented the repair of DNA damage and caused cells S/G2-arrest leading to MDA-MB-468 cells death.

Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.

Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer. The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis. In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.

Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate

Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate

In-silico design of novel potential HDAC inhibitors from indazole derivatives targeting breast cancer through QSAR, molecular docking and pharmacokinetics studies

Latest studies confirmed that abnormal function of histone deacetylase (HDAC) plays a pivotal role in formation of tumors and is a potential therapeutic target for treating breast cancer. In this research, in-silico drug discovery approaches via quantitative structure activity relationship (QSAR) and molecular docking simulations were adapted to 43 compounds of indazole derivatives with HDAC inhibition for anticancer activity against breast cancer. The QSAR models were built from multiple linear regression (MLR), and models predictability was cross-validated by leave-one-out (LOO) method. Based on these results, compounds C32, C26 and C31 from model 3 showed superior inhibitory activity with pIC50 of 9.30103, 9.1549 and 9.1549. We designed 10 novel compounds with molecular docking scores ranging from −7.9 to −9.3 kcal/mol. The molecular docking simulation results reveal that amino acid residues ILE1122 and PRO1123 play a significant role in bonding with 6CE6 protein. Furthermore, newly designed compounds P5, P2 and P7 with high docking scores of −9.3 kcal/mol, −8.9 kcal/mol and −8.8 kcal/mol than FDA-approved drug Raloxifene (-8.5 kcal/mol) and aid in establishment of potential drug candidate for HDAC inhibitors. The in-silico ADME functionality is used in the final phase to evaluate newly designed inhibitors as potential drug candidates. The results suggest that newly designed compounds P5, P2 and P7 can be used as a potential anti-breast cancer drug candidate.

Microfluidic nanoprecipitation of PEGylated PLGA nanoparticles with rapamycin and performance evaluation

Rapamycin (RAP) is currently being developed as potential antibreast cancer drug. However, its poor solubility completely limits its use. The aim of this study was to develop polyethylene glycol-poly(lactide-co-glycolide) (PEG-PLGA)-based nanoparticles (NPs) to load RAP via microfluidics with an appropriate polyethylene glycol (PEG) content to enhance the bioavailability of RAP. Polydimethylsiloxane (PDMS) chips with a Y-shaped channel were designed to obtain RAP-loaded PEG-PLGA NPs (RAP-PEG-PLGA). The entrapment efficiency (EE) and drug loading (DL) as well as release profile of RAP-PEG-PLGA were evaluated, and their resistance to plasma albumin adsorption of NPs with different PEG contents was evaluated and compared. RAW264.7 and 4T1 cells were used to assess the antiphagocytic and anticancer cells effect of NPs, respectively. RAP-PEG-PLGA of around 124 nm in size were successfully prepared with the EE of 82.0% and DL of 12.3%, and sustained release for around 40 d. A PEG relative content of 10% within the PEG-PLGA molecule was shown superior in resisting protein adsorption. RAP-PEG-PLGA inhibited the growth of breast cancer cells when the concentration was over 10 μg/mL, and the inhibition efficiency was significantly higher than free RAP. Hence, the current RAP-PEG-PLGA could be a potential therapeutic system for breast cancer treatment.

Oxidative versus Reductive Stress in Breast Cancer Development and Cellular Mechanism of Alleviation: A Current Perspective with Anti-breast Cancer Drug Resistance.

Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and - catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.