Drug For Breast Cancer Therapy Research Articles

Design and In-silico Study of ¹³¹Iodium Radiolabeled of Thiourea derivatives for Breast Cancer Treatment

Breast cancer is a serious challenge in both developed and developing countries, with current therapies still limited and potentially producing adverse side effects. To optimize breast cancer drug development, this study adopted an in-silico design approach. The aim is to develop radiopharmaceutical drugs with minimal side effects. Methods involved molecular docking analysis, molecular dynamics, drug scan, and pharmacokinetic profile prediction of the original ligan as well as the radioligand. Results showed that the radioligand had better binding energy and inhibition constant than tamoxifen as a comparator drug which is -11.31 kcal/mol and 0.00511 µM. Molecular dynamics analysis revealed that the radioligand compound exhibits comparable RMSD, RMSF, and stability metrics to the native ligand at the GRPR receptor with average RMSD and RMSF of 5.263 Å and 2.285 Å, respectively. By considering the results of these various methods, the radioligand compound shows potential as an effective radiopharmaceutical drug in breast cancer therapy.

Co-Encapsulation of Paclitaxel and Doxorubicin in Liposomes Layer by Layer

The synergistic effect of antineoplastic drug co-encapsulation systems has made them highly regarded due to their improved pharmacological efficacy. Biopolymer-coated liposomes were evaluated for paclitaxel and doxorubicin co-encapsulation in MCF-7 and MDA-MB-231 breast cancer cell lines. These nanosystems are characterized by dynamic light scattering, transmission electron microscopy, and UV–VIS spectroscopy. The conventional and hybrid liposomal systems presented sizes of 150 to 230 nm and %EE greater than 80% for the encapsulated active ingredients. These drug-laden liposomal systems significantly decreased cell viability in both breast cancer cell lines compared with liposome-free drugs. The delivery of antineoplastic drugs in breast cancer therapy could potentially benefit from new hybrids for drug co-encapsulation.

Secondary metabolite profiling using HR-LCMS, antioxidant and anticancer activity of Bacillus cereus PSMS6 methanolic extract: In silico and in vitro study

Novel anticancer drugs of natural origin have increased tremendously due to the resistance of multiple chemotherapeutic drugs in breast cancer therapy and their high toxicity with undesirable side effects. The study investigates the bioactivity of secondary metabolites derived from Bacillus cereus PSMS6 isolated from marine soil sediment in the Velar estuary, Parangepattai, Cuddalore district, Tamil Nadu, and India. Strains were isolated and antagonistic activity was screened using the agar well diffusion method. B. cereus PSMS6 exhibited potency, and its crude extract was tested for antioxidant, anticancer, and cytotoxic MTT assay potential. The methanolic extract of B. cereus PSMS6 was analyzed by mass spectrometry HRLC-MS and FT-IR to determine the bioactive compounds. A drug interaction study with the anti-breast cancer protein HER2 was performed by molecular docking analysis. Antioxidant activities were determined using total antioxidant scavenging assay, ABTS and DPPH free radical scavenging assays. The total antioxidant scavenging assay of the crude extract of B. cereus methanol had an IC50 value of 28.33±1.01, in ABTS IC50 value of the extract was 29.00±0.28 and in DPPH the IC50 of the extract was 34.91±0.09. The negative ion compound Palmitoylglycerone phosphate had a LibDock score of 149.487 and the positive ion compound N5-(4-Methoxybenzyl) glutamine had 120.116. These compounds show promising anticancer activity. The current study reported that the bioactive secondary metabolite of B. cereus PSMS6 retains anti-cancer, and antioxidant properties. This is the first report to show the production of the Palmitoylglycerone phosphate metabolite from B. cereus PSMS6.

Upregulation of MHC I antigen processing machinery gene expression in breast cancer cells by Trichostatin A

Epigenetic alterations associated with cancer have been shown to facilitate tumorigenesis and promote metastasis. In the study of cancer metastasis, epigenetics has been revealed to play a crucial role in supporting tumour immune evasion. As a result, epigenetic drugs have been identified as potential agents to activate anti-tumour immune responses and reverse tumour immunologically tolerant states. Mounting evidence is showing aberrant expression of MHC class I antigen processing molecules in cancers and their upregulation as a potential indicator for anti-tumour immunity. In this study, we demonstrate that the epigenetic drug Trichostatin A (TSA), a histone deacetylase inhibitor, can restore MHC I antigen presentation machinery (MHC I APM) genes in human breast cancer cells (MCF-7). Treatment with TSA resulted in the upregulation of MHC I, B2M, and PSMB9 in MCF-7 monolayer cells, and MHC I, B2M, PSMB9, PSMB8, TAP1, and TAP2 in MCF-7 spheroid cells. Interestingly, treatment with TSA also increased CD274 expression in these cells and enhanced the invasion ability of the MCF-7 spheroid. This aggressive behaviour was confirmed by increased expression of metastatic-related genes, SCN5A (nNav1.5 protein) and MMP1. In summary, although the restoration of MHC I APM expression was achieved by TSA, the upregulation of metastatic genes and CD274 also enhanced the invasion ability of breast cancer cells. These findings suggest the need for careful consideration when utilizing epigenetic drugs for breast cancer therapy.

Abstract B030: ABC101-1, a novel microtubule inhibitor antibody-drug conjugate targeting HER2, has potent anti-tumor activity in a breast cancer model

Abstract Background: ABC101-1 is an antibody-drug conjugate (ADC) targeting receptor tyrosine-protein kinase erbB-2, also known as HER2. ABC101-1 consists of a humanized IgG1 monoclonal antibody called trastuzumab conjugated to a microtubulin inhibitor, DM1, through interchain cysteines with a drug-to-antibody ratio (DAR) of 8. Our novel non-cleavable linker platform using maleimide as a connector enabled the construction of homogeneous ABC101-1 with DAR of 8, via a straightforward process resulting in high conjugation yield. Employing non-cleavable linkers may ensure that the cytotoxic drug is delivered stably to tumor cells, enhancing the therapeutic efficacy of ADC. Herein, we describe anti-breast cancer activity through in vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and binding affinity of ABC101-1. Methods: In vitro cytotoxicity of ADC and linker-payload was evaluated by measuring cell viability using Cell Count Kit-8 (CCK8) analysis. In vivo anti-tumor activity was investigated using SKBR3 cell line-derived xenograft (CDX) model. A pharmacokinetic (PK) profile was assessed by performing indirect ELISA to determine concentrations of total mAb in the serum. The binding affinity of ABC101-1 to HER2 protein was assessed using the indirect ELISA measuring the concentrations of total mAb. Results: In this study, ABC101-1 exhibited potent in vitro cytotoxicity with picomolar activity on HER2-positive breast cancer cell line. In the CDX breast cancer model, ABC101-1 led to stronger tumor growth inhibition in both early and late phases than ado-trastuzumab emtansine (DAR 3.5) at the same dose. Also, the favorable pharmacokinetic profile of ABC101-1 was observed, along with the preserved antigen-binding ability upon the conjugation to linker-payload. Conclusions: ABC101-1 displayed preclinical efficacy in in vitro and in vivo studies as well as a favorable PK, thereby suggesting its therapeutic potential as an anti-tumor drug in breast cancer therapy. This study would reveal that our novel linker platform is a promising and efficient strategy to develop effective and homogeneous ADCs with DAR 8. Our finding may support the further pre-clinical evaluation of ABC101-1. Citation Format: Seo Woo Kim, Hana Yu, Geon Ho Lee, Tae Gyu Lim, Minji Jeong, Hyeonjoo Hwang, Jee Eun Moon, Yong Beom Lee, Sung-Ha Jin, Jin Hyun Jeong. ABC101-1, a novel microtubule inhibitor antibody-drug conjugate targeting HER2, has potent anti-tumor activity in a breast cancer model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B030.

Calcium Influx Pathways in Breast Cancer: Opportunities for Pharmacological Intervention

Numerous cellular processes, including the release of neurotransmitters and the contraction of muscles, are largely triggered and regulated by Ca2+ inflow via Ca2+ permeable ion channels. In addition, Ca2+ influx regulates cellular migration and proliferation, two mechanisms linked to cancer. This study focuses on calcium influx in breast cancer cells and discusses how future drugs for breast cancer therapy may be pharmacological modulators of particular Ca2+ influx channels. Certain breast tumors have altered expression of particular calcium permeable ion channels. Such alterations may occasionally be connected to the prognosis and subtype of breast cancer. These days, models both in vivo and in vitro have assisted in identifying particular Ca2+ channels that are crucial for the growth and invasiveness of of cancerous breast cells. Nonetheless, additional research is still needed to fully understand several features of Ca2+ influx in breast cancer. These include figuring out the processes behind the changed expression and the best treatment plan to target breast cancer cells via particular Ca2+ channels. In the upcoming ten years, research should concentrate on the function of Ca2+ influx in mechanisms other than the migration and proliferation of breast cancer cells.

Pharmacological Therapeutic Potential in Breast Cancer through Calcium Influx Pathways

Numerous cellular processes, including the release of neurotransmitters and the contraction of muscles, are largely triggered and regulated by Ca2+ inflow via Ca2+ permeable ion channels. In addition, Ca2+ influx regulates cellular migration and proliferation, two mechanisms linked to cancer. This study focuses on calcium influx in breast cancer cells and discusses how future drugs for breast cancer therapy may be pharmacological modulators of particular Ca2+ influx channels. Certain breast tumors have altered expression of particular calcium permeable ion channels. Such alterations may occasionally be connected to the prognosis and subtype of breast cancer. These days, models both in vivo and in vitro have assisted in identifying particular Ca2+ channels that are crucial for the growth and invasiveness of cancerous breast cells. Nonetheless, additional research is still needed to fully understand several features of Ca2+ influx in breast cancer. These include figuring out the processes behind the changed expression and the best treatment plan to target breast cancer cells via particular Ca2+ channels. In the upcoming ten years, research should concentrate on the function of Ca2+ influx in mechanisms other than the migration and proliferation of breast cancer cells

Advances in Targeted Therapy of Breast Cancer with Antibody-Drug Conjugate.

Antibody-drug conjugates (ADCs) are a potential and promising therapy for a wide variety of cancers, including breast cancer. ADC-based drugs represent a rapidly growing field of breast cancer therapy. Various ADC drug therapies have progressed over the past decade and have generated diverse opportunities for designing of state-of-the-art ADCs. Clinical progress with ADCs for the targeted therapy of breast cancer have shown promise. Off-target toxicities and drug resistance to ADC-based therapy have hampered effective therapy development due to the intracellular mechanism of action and limited antigen expression on breast tumors. However, innovative non-internalizing ADCs targeting the tumor microenvironment (TME) component and extracellular payload delivery mechanisms have led to reduced drug resistance and enhanced ADC effectiveness. Novel ADC drugs may deliver potent cytotoxic agents to breast tumor cells with reduced off-target effects, which may overcome difficulties related to delivery efficiency and enhance the therapeutic efficacy of cytotoxic cancer drugs for breast cancer therapy. This review discusses the development of ADC-based targeted breast cancer therapy and the clinical translation of ADC drugs for breast cancer treatment.

Construction of Fe-doped ZIF-8/DOX nanocomposites for ferroptosis strategy in the treatment of breast cancer.

Breast cancer has become one of the top five commonest causes of cancer death. The use of ferroptosis to induce the generation of reactive oxygen species (ROS) in cancer cells presents a promising and potential strategy for cancer treatment. Herein, a series of facile bimetallic nanoparticles (x% Fe-doped ZIF-8) were synthesized and tested, and doxorubicin (DOX), a classic drug for breast cancer therapy, was encapsulated. After comparing the ratios of Fe2+/(Fe2+ + Zn2+), 7% Fe-doped ZIF-8 (7FZ) was found to be the most suitable particle for medical application. The drug loading efficiency of DOX@7FZ was 58.01 ± 0.02%. The pH-sensitive DOX@7FZ was degraded and DOX was released in lysosomes once internalized. Both the intracellular content of iron and ROS increased significantly. Meanwhile, the cell viability declined to 13.98% in 24 h at a concentration of 60 μg mL-1 and the IC50 was 42.68 μg mL-1. Moreover, the expression of Bcl-2 and GPX-4 proteins decreased in a time-dependent manner, indicating that DOX@7FZ was able to enhance the ROS level in cancer cells via a synergistic effect between apoptosis and ferroptosis. The mechanism of action of DOX@7FZ was further verified using hematoxylin and eosin staining and immunohistochemical staining of Bcl-2 and GPX-4. These remarkable characteristics of DOX@7FZ may inspire further advancements in the treatment of breast cancer.

Crosstalk between Methylation and ncRNAs in Breast Cancer: Therapeutic and Diagnostic Implications

Breast cancer, as a highly heterogeneous malignant tumor, is one of the primary causes of death among females worldwide. The etiology of breast cancer involves aberrant epigenetic mechanisms and abnormal expression of certain non-coding RNA (ncRNAs). DNA methylation, N6-methyladenosine(m6A), and histone methylation are widely explored epigenetic regulation types in breast cancer. ncRNAs are a group of unique RNA transcripts, mainly including microRNA (miRNAs), long non-coding RNA (lncRNAs), circular RNA (circRNAs), small interfering RNA (siRNAs), piwi-interacting RNA (piRNAs), etc. Different types of methylation and ncRNAs mutually regulate and interact to form intricate networks to mediate precisely breast cancer genesis. In this review, we elaborate on the crosstalk between major methylation modifications and ncRNAs and discuss the role of their interaction in promoting breast cancer oncogenesis. This review can provide novel insights into establishing a new diagnostic marker system on methylation patterns of ncRNAs and therapeutic perspectives of combining ncRNA oligonucleotides and phytochemical drugs for breast cancer therapy.

Molecular Docking and in silico Pharmacological Screening of Oleosin from Cocos Nucifera Complexed with Tamoxifen in Developing Potential Breast Chemotherapeutic Leads.

Tamoxifen is a widely used drug for breast cancer therapy; however, concerns and controversies regarding its efficiency arise as it induces various side effects, including endometrial cancer. This study aimed to assess the application of Oleosin as a potential protein carrier of Tamoxifen by evaluating the pharmacokinetic and pharmacological properties of Tamoxifen and determining its intermolecular interactions with Oleosin through in silico techniques. The pharmacokinetic and pharmacological properties of Tamoxifen were assessed by using predictive applications such as SwissADME, PaccMann, and Way2Drug. On the other hand, Oleosin does not have a crystal structure in PDB. Thus, homology modeling was done through SWISS-MODEL to obtain a structure. The interactions between Oleosin (Accession no.: AZZ09171.1) and Tamoxifen (PubChem ID: 2733526) were studied by performing molecular docking using AutoDock4 to determine their feasibility as breast cancer drug combinations. The chosen structure of Oleosin from the homology modeling resulted in an RMSD of 1.80Å. Tamoxifen was predicted to have the highest activity in MCF7 cell lines, direct interaction with cytochrome enzymes, mediated interaction with estrogen receptors and tyrosine-protein kinase FYN, and low toxicity hazards based on the acute rat toxicity assay. It has lowest binding affinity of -5.26 kcal/mol. The hydrophobic (Ala106, Leu77, Ile80, Val84, and Tyr81) and electrically charged (Lys107 and Asp108) amino acids were critical in binding in the Oleosin-Tamoxifen-complex. Heatmap revealed that phenyl, ether, amine, and alkenyl are the functional groups involved in the receptor-ligand interactions. The application of Oleosin as a potential drug carrier was demonstrated by assessing the intermolecular interactions between the Tamoxifen and Oleosin through molecular docking. The properties of Tamoxifen revealed that the molecular targets impact the efficiency and the mechanism of action of the drug. This can also be the basis for investigating and determining the serious adverse effects induced by the drug.

PH-Responsive Chitosan-Adorned Niosome Nanocarriers for Co-Delivery of Drugs for Breast Cancer Therapy

pH-Responsive Chitosan-Adorned Niosome Nanocarriers for Co-Delivery of Drugs for Breast Cancer Therapy

Folic Acid-Decorated pH-Responsive Nanoniosomes With Enhanced Endocytosis for Breast Cancer Therapy: In Vitro Studies.

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. The purpose of this study is a targeted delivery toward in vitro (on MCF7 and 4T1 breast cancer cell lines) through niosomes-based nanocarriers. To this end, different bioactive molecules, including hyaluronic acid (HA), folic acid (FA), and polyethylene glycol (PEG), were used and compared for surface modification of niosomes to enhance endocytosis. FA-functionalized niosomes (Nio/5-FU/FA) were able to increase cell cytotoxicity and reduce cell migration and invasion compared to PEG-functionalized niosomes (Nio/5-FU/PEG), and HA-functionalized niosomes (Nio/5-FU/HA) groups in MCF-7 and 4T1 cell lines. Although the Nio/5-FU/PEG and Nio/5-FU/HA demonstrated MCF7 cell uptake, the Nio/5-FU/FA exhibited the most preponderant endocytosis in pH 5.4. Remarkably, in this study 5-FU loaded niosomes (nonionic surfactant-based vesicles) were decorated with various bioactive molecules (FA, PEG, or HA) to compare their ability for breast cancer therapy. The fabricated nanoformulations were readily taken up by breast cancer cells (in vitro) and demonstrated sustained drug release characteristics, inducing cell apoptosis. Overall, the comprehensive comparison between different bioactive molecules-decorated nanoniosomes exhibited promising results in finding the best nano formulated candidates for targeted delivery of drugs for breast cancer therapy.

Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation.

Breast cancer is the most common cancer of women—it affects more than 2 million women worldwide. PTP1B phosphatase can be one of the possible targets for new drugs in breast cancer therapy. In this paper, we present new curcumin derivatives featuring a 4-piperidone ring as PTP1B inhibitors and ROS inducers. We performed cytotoxicity analysis for twelve curcumin derivatives against breast cancer MCF-7 and MDA-MB-231 cell lines and the human keratinocyte HaCaT cell line. Furthermore, because curcumin is a known antioxidant, we assessed antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the potential binding mode of new inhibitors within the allosteric site of the enzyme. We observed that two tested compounds are better anticancer agents than curcumin. Moreover, we suggest that blocking the -OH group in phenolic compounds causes an increase in the cytotoxicity effect, even at a low concentration. Furthermore, due to this modification, a higher level of ROS is induced, which correlates with a lower level of PTP1B.

High-Throughput In Vitro Gene Expression Profile to Screen of Natural Herbals for Breast Cancer Treatment.

Breast cancer has surpassed lung cancer as the most commonly diagnosed cancer in women worldwide. Some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in breast cancer. However, the chemical composition and underlying anti-tumor mechanisms of TCM still need to be investigated. The primary aim of this study is to provide unique insights to screen the natural components for breast cancer therapy using high-throughput transcriptome analysis. Differentially expressed genes were identified based on two conditions: single samples and groups were classified according to their pharmaceutical effect. Subsequently, the sample treated with E. cochinchinensis Lour. generated the most significant DEGs set, including 1,459 DEGs, 805 upregulated and 654 downregulated. Similarly, group 3 treatment contained the most DEGs (414 DEGs, 311 upregulated and 103 downregulated). KEGG pathway analyses showed five significant pathways associated with the inflammatory and metastasis processes in cancer, which include the TNF, IL−17, NF-kappa B, MAPK signaling pathways, and transcriptional misregulation in cancer. Samples were classified into 13 groups based on their pharmaceutical effects. The results of the KEGG pathway analyses remained consistent with signal samples; group 3 presents a high significance. A total of 21 genes were significantly regulated in these five pathways, interestingly, IL6, TNFAIP3, and BRIC3 were enriched on at least two pathways, seven genes (FOSL1, S100A9, CXCL12, ID2, PRS6KA3, AREG, and DUSP6) have been reported as the target biomarkers and even the diagnostic tools in cancer therapy. In addition, weighted correlation network analysis (WGCNA) was used to identify 18 modules. Among them, blue and thistle2 were the most relevant modules. A total of 26 hub genes in blue and thistle2 modules were identified as the hub genes. In conclusion, we screened out three new TCM (R. communis L., E. cochinchinensis Lour., and B. fruticosa) that have the potential to develop natural drugs for breast cancer therapy, and obtained the therapeutic targets.

Antiangiogenic therapy for breast cancer with triple negative phenotype

Triple-negative breast cancer is 1024% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

Evolving insight of adverse drug reaction associated with breast cancer drugs

Cancer begins when genes mutate and cause cell proliferation in an uncontrollable manner. Breast cancer develops in females in the lobules and ducts of breast cells. As per the American Institute of Cancer Research, Breast cancer is diagnosed as the second leading cause of death in women if not noticed at the early stages of treatment. In recent decades, the widespread awareness and improvements in the screening and treatment of breast cancer have lowered the mortality rate of breast cancer by 40%. However, drugs for breast cancer therapy do carry adverse effects. Worldwide efforts are ongoing to detect and to neutralize these adverse effects. That is why it is inevitable to bring it to the notice of physicians through adverse drug reaction monitoring of anticancer drugs. This paper explores some of the variables causing these ADRs in the individual case reports that has been assembled via different renowned journal databases such as Google Scholar, Science Direct, Cochrane Library & PubMed. Accustomized breast cancer medications such as5-fluorouracil, cisplatin, sunitinib, doxorubicin, cyclophosphamide, & topotecanare being used in the treatment of breast cancer. A specific approach to monitor the ADR is necessary to deal with them. This review addresses the complexity of the ADRs that can subsequently be used by the clinicians who are serving in the tertiary health care system.

Anticancer evaluation of N-benzoyl-3-allylthiourea as potential antibreast cancer agent through enhances HER-2 expression.

Breast cancer with HER-2 overexpression is sensitive to drugs which target the receptor or its kinase activity. Although the anti-HER-2 therapies commonly used have improved patient outcome, resistance usually occurs. In this present study, we investigated a modification of the chemical structure of allylthiourea derivatives in order to enhance the cytotoxicity effect on breast cancer cells with HER-2 overexpression. The aim of this research was to predict the absorption, distribution, metabolism, excretion, and toxicity by in silico study and to explore the effect N-benzoyl-3-allylthiourea (BATU) on MCF-7 cell line with overexpressing of HER-2 using MTT assay and western blot. The result showed that the cytotoxicity effects of BATU on MCF-7/HER-2 cell line (IC50 value 0.64 mM) were higher than on MCF-7 cell lines (IC50 value 1.47 mM). In addition, the cytotoxic effects of BATU on MCF-7 and MCF-7/HER-2 were higher than allylthiourea as a lead compound (IC50 value 5.22 and 3.17 mM). The results also confirmed that the BATU compound has the ability to effectively enhance its cytotoxicity against MCF-7/HER-2 through enhanced HER-2 expression and inhibition of nuclear factor kappa B (NF-kB) activation. Above all, the BATU compound is effective in increasing HER-2 expression and inactivating NF-kB transcription factors, thereby resulting in inhibition of protein expression which works a significant part in cell proliferation. Therefore, the BATU compound has the potential to be developed as a complementary drug in breast cancer therapy with HER-2 positive.

Bioinformatic Analysis Reveals GSG2 as a Potential Target for Breast Cancer Therapy.

ObjectiveTo explore the potential role of GSG2 in breast cancer progression.MethodsThe mRNA expression, DNA copy number and clinical data used in this study were obtained from the TCGA data portal. The copy number variations (CNVs) thresholds were determined according to the set of discrete copy number calls provided by Genomic Identification of Significant Targets in Cancer (GISTIC).ResultsThe mRNA expression level of GSG2 in 112 breast cancer tissues was much higher than that in adjacent normal tissues. GSG2 was significantly upregulated in stage II compared with stage I, and there was no differential expression of GSG2 between tumors with or without metastasis. Heterozygous deletion occupied 57.1% of CNVs for GSG2 gene in breast cancer samples. Patients with higher GSG2 expression tended to suffer from poorer prognosis.ConclusionOur profiling analysis indicated the overexpression of GSG2 might play an important role in breast cancer development, suggesting that GSG2 could be a new target for breast cancer treatment, making GSG2 inhibitors becoming potential drugs for breast cancer therapy.

Novel multifunctional triple folic acid, biotin and CD44 targeting pH-sensitive nano-actiniaes for breast cancer combinational therapy

In this study, novel multifunctional folic acid, biotin, and CD44 receptors targeted and pH-sensitive “nano-actiniaes” were fabricated with icariin (ICA) and curcumin (Cur) as loaded model drugs for breast cancer therapy. The newly synthesized polymer oligomeric hyaluronic acid-hydrazone bond-folic acid-biotin (Bio-oHA-Hyd-FA) was characterized by 1H NMR spectrogram (proton nuclear magnetic resonance). The obtained drug carrier Bio-oHA-Hyd-FA self-assembled into nanomicelles, named as “nano-actiniaes”, in aqueous media with hydrodynamic diameter of 162.7 ± 5 nm. The size, surface zeta potential, and morphology of the “nano-actiniaes” were observed via TEM. The in vitro release experiment indicated that much more encapsulated icariin (ICA) and curcumin (Cur) were released from the Bio-oHA-Hyd-FA micelles (nano-actiniaes) in the acidic environment. Additionally, the cytotoxicity research demonstrated that the Bio-oHA-Hyd-FA carrier material was completely nontoxic, and the ICA&Cur “nano-actiniaes” had greater cytotoxicity compared with other control groups. In addition, the “nano-actiniaes” were found to significantly inhibit cancer cell invasion by Transwell assay. Moreover, in vivo evaluation of anti-tumor effect illustrated that the ICA and Cur “nano-actiniaes” possessed inhibitory effect on tumors. Consequently, the multi-targeted pH-sensitive “nano-actiniaes” can realize significant tumor targeting and effectively inhibit tumor growth.