scholarly journals Arthrospira platensis Mediated Biosynthesis of Silver Nanoparticles as Breast Cancer Proliferation and Differentiation Controlling agent: In-vitro and In-vivo Safety Approach

2021 ◽  
Author(s):  
Nehal El Deeb ◽  
Mai Abo-Eleneen ◽  
Omyma Awad ◽  
Atef Aboshady
Keyword(s):  
Breast Cancer ◽  
Silver Nanoparticles ◽  
Arthrospira Platensis ◽  
Mice Model ◽  
Cancer Proliferation ◽  
Protein Marker ◽  
Ki 67 ◽  
Protein Levels

Abstract Biogenic Silver nanoparticles (AgNPs) are one of the most fascinating nanomaterials used in biomedical purposes. In the current study, we biosynthesized AgNPs using Arthrospira platensis, Microcystis aeruginosa and Chlorella vulgarisactive metabolites and evaluate their efficacy against breast cancer. The recovered AgNPs was characterized using scanning and transmission electron microscopy (SEM and TEM). The safety usage of bio-AgNPs was tested in-vitro on PBMCs cells and in-vivo. The obtained results indicated the safety usage of bio-AgNPs at concentration 0.1 mg/ml on PBMCs cells and 1.5mg/ml on the tested Albino mice. The bio-AgNPs displayed dose-dependent cytotoxicity (0.1 mg/ml) against HepG-2, CaCO-2 and MCF-7 cell lines via ROS induction and arresting treated cells in G0/G1 and sub G0 phases. In addition, Arthrospira bio-AgNPs treatment induced cellular apoptosis in breast cancer cells via the down regulation of survivin, MMP7, TGF and Bcl2 genes expressions. Upon Arthrospira bio-AgNPs treatment, a great delay in tumor growth and prolonged survival were recorded in breast cancer mice model. Furthermore, after Arthrospira bio-AgNPs treatment, a great reduction in Ki 67 protein marker from 60% to be 20% and was recorded and an elevation in Caspase 3 protein levels was recorded in treated groups with percentage 65% comparing with 45% in Doxorubicin treated groups.

Arthrospira Platensis Mediated Green Biosynthesis of Silver Nanoparticlesas Breast Cancer Controlling Agent: In-vitro and In-vivo Safety Approach.

2021 ◽  
Author(s):  
Nehal El Deeb ◽  
Mai A. Abo-Eleneen ◽  
Omyma A. Awad ◽  
Atef M. Abo-Shady
Keyword(s):  
Breast Cancer ◽  
Survival Rates ◽  
Arthrospira Platensis ◽  
Active Metabolites ◽  
Protein Marker ◽  
Anticancer Efficacy ◽  
Protein Levels ◽  
Albino Mice

Abstract Biogenic Silver Nanoparticle (bio-AgNPs) is one of the most fascinating nanomaterials used in the biomedical purposes. In the current study, we biosynthesized AgNPs (bio-AgNPs) using Arthrospira platensis(A-bio-AgNPs), Microcystis aeruginosa(M-bio-AgNPs)and Chlorella vulgaris(C-bio-AgNPs) active metabolites and evaluated their anticancer efficacy against breast cancer. The recovered bio-AgNPs were characterized using Scanning and Transmission Electron Microscopy (SEM and TEM) and their safety profiles were monitoring in-vitro on PBMCs cells and in-vivo on Albino mice. The obtained results indicated the safety usage of bio-AgNPs at concentration of 0.1 mg/ml on PBMCs cells and 1.5mg/ml on the Albino mice. The bio-AgNPs displayed dose-dependent cytotoxic effects against HepG-2, CaCO-2 and MCF-7 cell lines by inducing ROS and arresting the treated cells in G0/G1 and sub G0 phases. In addition, A-bio-AgNPs induced breast cancer cellular apoptosis by down regulating the expression of survivin, MMP7, TGF and Bcl2 genes. Upon A-bio-AgNPs treatment, a significant reduction in tumor growth and prolonged survival rates were recorded in breast cancer BALB/c model. Furthermore, A-bio-AgNPs treatment significant decreased theKi 67 protein marker from 60% (in the untreated group) to 20% and increased Caspase 3 protein levels to 65% (in treated groups) comparing with 45% (in Doxorubicin treated groups).

scholarly journals Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Xian Du ◽  
Yi-Hong Luo ◽  
Si-Jia Zhang ◽  
Biao Wang ◽  
Cong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
High Risk Group ◽  
Clinical Samples ◽  
Binding Motif ◽  
Ki 67 ◽  
Tissue Samples

Abstract Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

Co-loading of an anthracycline analogue Pirarubicin and Salinomycin in a 1:3 ratio into Quatramerbiodegradable polymeric nanoparticles synergistically inhibit growth of triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
Surender Kharbanda ◽  
Anees Mohammad ◽  
Sachchidanand Tiwari ◽  
Neha Mehrotra ◽  
Sireesh Appajosyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancers ◽  
Mice Model ◽  
Single Drug ◽  
Tnbc Cell ◽  
Dual Drug

e15047 Background: Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and differ from other types of invasive breast cancers in that they grow and spread faster. TNBCs have limited treatment options and a worse prognosis. Therapy with anthracyclines considered to be one of the most effective agents in the treatment. Unfortunately, resistance to anthracycline therapy is very common due to drug efflux mediated by overexpression of ABC transporter. Pirarubicin (PIRA), an analogue of doxorubicin (DOX), is approved in Japan, Korea and China and is shown to be less cardiotoxic than DOX. Recent studies suggest that cancer stem cells (CSCs) play an important role in tumorigenesis and biology of TNBC. Targeting CSCs may be a promising, novel strategy for the treatment of this aggressive disease. Recent studies have shown that salinomycin (SAL) preferentially targets the viability of CSCs. Methods: SAL and PIRA were co-encapsulated in polylactic acid (PLA)-based block copolymeric nanoparticles (NPs) to efficiently co-deliver these agents to treat TNBC cells. Results: Generated SAL-PIRA co-encapsulated dual drug-loaded NPs showed an average diameter of 110 ± 7 nm, zeta potential of -12.5 mV and PDI of less than 0.25. Both of these anti-cancer agents showed slow and sustained release profile in non-physiological buffer (PBS, pH 7.4) from these dual drug-encapsulated NPs. Additionally, multiple ratios (PIRA:SAL = 3:1, 1:1, 1:3) were encapsulated to generate diverse dual drug-loaded NPs. The results demonstrate that, in contrast to 1:1 and 3:1, treatment of TNBC cells with 1:3 ratio of PIRA:SAL dual drug-loaded NPs, was associated with significant inhibition of growth in vitro in multiple TNBC cell lines. Interestingly, PIRA:SAL (1:3) was synergistic as compared to either SAL- or PIRA single drug-loaded NPs. The IC50 of PIRA and SAL in single drug-encapsulated NPs is 150 nM and 700 nM respectively in MDA-MB-468. Importantly, the IC50 of PIRA in dual drug-encapsulated NPs dropped down to 30 nM (5-fold). Similar results were obtained in SUM-149 TNBC cell line. Studies are underway to evaluate in vivo biological activity of PIRA:SAL (1:3) on tumor growth in a TNBC xenograft mice model. Conclusions: These results demonstrate that a novel dual drug-loaded NP formulation of PIRA and SAL in a unique ratio of 1:3 represents an approach for successful targeting of CSCs and bulk tumor cells in TNBC and potentially other cancer types.

scholarly journals CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 129
Author(s):  
Huinan Qu ◽  
Da Qi ◽  
Xinqi Wang ◽  
Yuan Dong ◽  
Qiu Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Suppressor Gene ◽  
Binding Motif ◽  
Cancer Proliferation ◽  
In Vivo Experiments

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

scholarly journals Overexpression of miRNA-3613-3p Enhances the Sensitivity of Triple Negative Breast Cancer to CDK4/6 Inhibitor Palbociclib

2020 ◽  
Vol 10 ◽  
Author(s):  
Yuanhang Yu ◽  
Han Liao ◽  
Rong Xie ◽  
Yue Zhang ◽  
Renjing Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
Predictive Biomarker ◽  
Inhibitory Effect ◽  
Breast Cancer Patients ◽  
Ki 67

Triple negative breast cancer (TNBC) is characterized by lack of expression of the estrogen and progesterone receptors and HER2, which are common therapeutic targets. CDK4/6 inhibitor Palbociclib has been approved as an anti-cancer agent for breast cancer. However, identifying biomarkers that predict the response to Palbociclib has always been a challenge for molecular targeted therapy. In this study, we identify microRNA as a hallmark in TNBC patients and explore if miR-3613-3p might serve as a tumor suppressor biomarker for triple negative breast cancer patients and if overexpression of miR-3613-3p could enhance the sensitivity of TNBC cells to Palbociclib. We show that the expression of miR3613-3p was down-regulated in TNBC tumors and cells, and the overexpression of miR-3613-3p in patients’ tumor tissues was clinically and pathologically correlated with favorable prognosis, such as smaller tumor size and the lower Ki-67. In vitro, overexpression of miR-3613-3p inhibited cell proliferation, induced G1 cell-cycle arrest, and enhanced the sensitivity of TNBC cells to Palbociclib treatment. In vivo study revealed that overexpression of miR-3613-3p inhibited TNBC tumorigenesis and exerted a significant inhibitory effect of Palbociclib on MDA-MB-231 cells. Mechanically, SMAD2 and EZH2 were found to be two direct targets of miR-3613-3p and mediate the proliferation of TNBC cells and the sensitivity of the cells to Palbociclib through inducing cellular senescence. Our findings suggested that miR-3613-3p acts as a cancer-suppressor miRNA in TNBC. Moreover, our study showed that miR-3613-3p might be used as a predictive biomarker for the response of TNBC to Palbociclib.

Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo

2010 ◽  
Vol 128 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Yi Chen ◽  
Edwin A. Alvarez ◽  
Diana Azzam ◽  
Seth A. Wander ◽  
Natalia Guggisberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Cancer Proliferation ◽  
Proliferation In Vitro

scholarly journals UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Chaohui Gu ◽  
Keyuan Zhao ◽  
Naichun Zhou ◽  
Feng Liu ◽  
Fei Xie ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Circular Rna ◽  
Cancer Proliferation ◽  
Lower Survival Rate ◽  
Protein Levels

Abstract Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan–Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3′UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.

scholarly journals Xiao-Ai-Ping Injection Enhances Effect of Paclitaxel to Suppress Breast Cancer Proliferation and Metastasis via Activating Transcription Factor 3

2020 ◽  
Vol 19 ◽  
pp. 153473542090646 ◽  
Author(s):  
Junjun Chen ◽  
Xiangqi Zhang ◽  
Xiao Xiao ◽  
Yawei Ding ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Experimental Studies ◽  
Underlying Mechanism ◽  
Activating Transcription Factor 3 ◽  
Antitumor Effects ◽  
Cancer Proliferation ◽  
Potential Strategy ◽  
Activating Transcription Factor

Chemotherapy is an effective treatment for invasive breast cancer. Paradoxically, many recently published findings showed that the first-line chemotherapeutic agent paclitaxel (PTX) showed pro-metastatic effects in the progress of treating breast cancer. Xiao-Ai-Ping (XAP) injection, composed of a traditional herbal medicine, Marsdenia tenacissimae extract, is known to exert antitumor effects on various cancers. However, there are few experimental studies on breast cancer. The underlying mechanism of the antitumor effect of XAP combined with chemotherapy agents has not been fully understood. In the present study, we sought to find the antitumor effects of XAP combined with PTX in vitro and in vivo. The data demonstrated that the combination of XAP with PTX resulted in remarkable enhancement of the pro-apoptotic, migration-inhibiting, and anti-invasive effects of PTX in vitro. Significantly, further study showed the overexpression of ATF3 in PTX-treated cell, while XAP counteracted the change of ATF3 induced by PTX. Moreover, it showed that combination treatment could promote the inhibition of tumor growth in MDA-MB-231 cell xenograft mouse model. Compared with PTX treatment, the downregulation of ATF3 indicated that ATF3 played a pivotal role in the combination of XAP with PTX to exert a synergistic effect. Overall, it is expected that PTX combined with XAP may serve as an effective agent for antitumor treatment, and dampening ATF3 maybe a potential strategy to improve the efficacy of PTX.

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