Lentivirus-mediated CDglyTK gene-modified free flaps by intra-artery perfusion show targeted therapeutic efficacy in rat model of breast cancer

Abstract Background Free flap-mediated gene therapy in the tumor bed following surgical resection is a promising approach in cancer targeted treatment of residual disease. We investigated the selective killing efficacy of a lentivirus-mediated cytosine deaminase-thymidine kinase (CDglyTK) gene in transplanted breast cancer delivered into a free flap by intra-artery perfusion. Methods Proliferation, apoptosis, and cell cycle of rat SHZ-88 breast cancer cells transfected with a lentivirus-mediated CD/TK gene were measured following treatment with ganciclovir and 5-flucytosine in vitro. A model of residual disease of breast cancer in a rat superficial inferior epigastric artery (SIEA) flap model was used to study the therapeutic potential of a double suicide CD/TK and prodrug system in vivo. Results Killing efficacy of the double suicide CD/TK and prodrug system on SHZ-88 cells was mediated by increased apoptosis and cell cycle arrest at the G1 phase with significant bystander effect. Following recombinant lentivirus transfection of rat SIEA flap by intra-artery perfusion, CD/TK gene expression was limited to the flap, and the volume and weight of transplanted tumors were significantly reduced without observable toxicity. Conclusions SIEA flaps transfected with a lentivirus-mediated CDglyTK gene by intra-artery perfusion effectively suppress transplanted breast tumor growth without obvious systemic toxic effects in rats.

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Phosphatidylserine-Gold Nanoparticles (PS-AuNP) Induce Prostate and Breast Cancer Cell Apoptosis

Pharmaceutics ◽

10.3390/pharmaceutics13071094 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1094

Author(s):

Allan Radaic ◽

Nam E. Joo ◽

Soo-Hwan Jeong ◽

Seong-II Yoo ◽

Nicholas Kotov ◽

...

Keyword(s):

Breast Cancer ◽

Gold Nanoparticles ◽

Biomedical Applications ◽

Therapeutic Potential ◽

Control Treatment ◽

Track Record ◽

Males And Females ◽

Breast And Prostate Cancer ◽

First Time

Prostate and breast cancer are the current leading causes of new cancer cases in males and females, respectively. Phosphatidylserine (PS) is an essential lipid that mediates macrophage efferocytosis and is dysregulated in tumors. Therefore, developing therapies that selectively restore PS may be a potential therapeutic approach for carcinogenesis. Among the nanomedicine strategies for delivering PS, biocompatible gold nanoparticles (AuNPs) have an extensive track record in biomedical applications. In this study, we synthesized biomimetic phosphatidylserine-caped gold nanoparticles (PS-AuNPs) and tested their anticancer potential in breast and prostate cancer cells in vitro. We found that both cell lines exhibited changes in cell morphology indicative of apoptosis. After evaluating for histone-associated DNA fragments, a hallmark of apoptosis, we found significant increases in DNA fragmentation upon PS-AuNP treatment compared to the control treatment. These findings demonstrate the use of phosphatidylserine coupled with gold nanoparticles as a potential treatment for prostate and breast cancer. To the best of our knowledge, this is the first time that a phosphatidylserine-capped AuNP has been examined for its therapeutic potential in cancer therapy.

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The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Nutrients ◽

10.3390/nu13041212 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1212

Author(s):

Getinet M. Adinew ◽

Equar Taka ◽

Patricia Mendonca ◽

Samia S. Messeha ◽

Karam F. A. Soliman

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Progression ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Therapeutic Potential ◽

Biological Activities ◽

Therapeutic Option ◽

Mesenchymal Transition ◽

Anticancer Effects

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

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The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0332 ◽

2016 ◽

Vol 41 (12) ◽

pp. 1303-1310 ◽

Cited By ~ 13

Author(s):

Guan-Yu Ren ◽

Chun-Yang Chen ◽

Wei-Guo Chen ◽

Ya Huang ◽

Li-Qiang Qin ◽

...

Keyword(s):

Cell Cycle ◽

Estrogen Receptor ◽

Benign Prostatic Hyperplasia ◽

G Protein ◽

Therapeutic Potential ◽

Prostatic Hyperplasia ◽

Docking Simulations ◽

G Protein Coupled

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

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Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

10.21203/rs.3.rs-210031/v1 ◽

2021 ◽

Author(s):

Xu Han ◽

Xiujuan Qu ◽

Beixing Liu ◽

Yizhe Wang ◽

Yang Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Molecular Docking ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Therapeutic Drug ◽

Specific Gene ◽

In Vivo Models

Abstract Background: Triple negative breast cancer (TNBC) is a tumor characterized by high recurrence and mortality, but without effective targeted therapy. It is urgent to explore new treatment strategy to improve the efficacy of TNBC therapy. Methods: Transcriptomic profiling datasets of TNBC were used for screening TNBC specific gene sets. Drug prediction was performed in Connectivity map (CMap) database. Molecular docking method was used for analyzing drug targets. In vitro and in vivo models of TNBC were constructed to examine the drug efficacy. Results: We screened out Mibefradil, a T-type Ca2+ channel blocker, might be a potential therapeutic drug for TNBC by transcriptomics and bioinformatics analysis, and verified that Mibefradil could inhibit the proliferation of TNBC cells by inducing apoptosis and cell cycle arrest. Furthermore, by network pharmacology and molecular docking analysis, AURKA was predicted as the most possible drug target of Mibefradil. Finally, it was proved that Mibefradil treatment could induce apoptosis by decreasing protein expression and phosphorylation level of AURKA in vitro and in vivo. Conclusions: Mibefradil played anti-cancer role in TNBC cells by targeting to AURKA to induce cell cycle and apoptosis. Our results repurposed Mibefradil as a potential targeted drug of TNBC and provided a fundamental research for a novel strategy TNBC treatment.

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Novel Platinum(II) Complexes Selectively Induced Apoptosis and Cell Cycle Arrest of Breast Cancer Cells In Vitro

ChemistrySelect ◽

10.1002/slct.201903290 ◽

2019 ◽

Vol 4 (44) ◽

pp. 12971-12977

Author(s):

Nenad Marković ◽

Milan Zarić ◽

Marija D. Živković ◽

Snežana Rajković ◽

Ivan Jovanović ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cycle Arrest ◽

Induced Apoptosis

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Biological Assessment of Laser-Synthesized Silicon Nanoparticles Effect in Two-Photon Photodynamic Therapy on Breast Cancer MCF-7 Cells

Nanomaterials ◽

10.3390/nano10081462 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1462

Author(s):

Ahmed Al-Kattan ◽

Lamiaa M. A. Ali ◽

Morgane Daurat ◽

Elodie Mattana ◽

Magali Gary-Bobo

Keyword(s):

Breast Cancer ◽

Photodynamic Therapy ◽

Silicon Nanoparticles ◽

Therapeutic Potential ◽

Light Stimulus ◽

Human Cancer ◽

Biological Assessment ◽

Two Photon ◽

Mcf 7

Driven by their distinctive physiological activities, biological properties and unique theranostic modalities, silicon nanoparticles (SiNPs) are one of the promising materials for the development of novel multifunctional nanoplatforms for biomedical applications. In this work, we assessed the possibility to use laser-synthesized Si NPs as photosensitizers in two-photon excited photodynamic therapy (TPE-PDT) modality. Herein, we used an easy strategy to synthesize ultraclean and monodispersed SiNPs using laser ablation and fragmentation sequences of silicon wafer in aqueous solution, which prevent any specific purification step. Structural analysis revealed the spherical shape of the nanoparticles with a narrow size distribution centered at the mean size diameter of 62 nm ± 0.42 nm, while the negative surface charge of −40 ± 0.3 mV ensured a great stability without sedimentation over a long period of time. In vitro studies on human cancer cell lines (breast and liver) and healthy cells revealed their low cytotoxicity without any light stimulus and their therapeutic potential under TPE-PDT mode at 900 nm with a promising cell death of 45% in case of MCF-7 breast cancer cells, as a consequence of intracellular reactive oxygen species release. Their luminescence emission inside the cells was clearly observed at UV-Vis region. Compared to Si nanoparticles synthesized via chemical routes, which are often linked to additional modules with photochemical and photobiological properties to boost photodynamic effect, laser-synthesized SiNPs exhibit promising intrinsic therapeutic and imaging properties to develop advanced strategy in nanomedicine field.

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Elacestrant (RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors

Breast Cancer Research ◽

10.1186/s13058-019-1230-0 ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 9

Author(s):

Hitisha K. Patel ◽

Nianjun Tao ◽

Kyung-Min Lee ◽

Mariela Huerta ◽

Heike Arlt ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Estrogen Receptor ◽

De Novo ◽

Single Agent ◽

Metastatic Breast ◽

Cancer Resistance ◽

Treatment Paradigm ◽

Anti Tumor Activity

Abstract Background Addition of CDK4/6 inhibitors (CDK4/6i) to endocrine therapy significantly increased progression-free survival, leading to their approval and incorporation into the metastatic breast cancer treatment paradigm. With these inhibitors being routinely used for patients with advanced estrogen receptor-positive (ER+) breast cancer, resistance to these agents and its impact on subsequent therapy needs to be understood. Considering the central role of ER in driving the growth of ER+ breast cancers, and thus endocrine agents being a mainstay in the treatment paradigm, the effects of prior CDK4/6i exposure on ER signaling and the relevance of ER-targeted therapy are important to investigate. The objective of this study was to evaluate the anti-tumor activity of elacestrant, a novel oral selective estrogen receptor degrader (SERD), in preclinical models of CDK4/6i resistance. Methods Elacestrant was evaluated as a single agent, and in combination with alpelisib or everolimus, in multiple in vitro models and patient-derived xenografts that represent acquired and “de novo” CDK4/6i resistance. Results Elacestrant demonstrated growth inhibition in cells resistant to all three approved CDK4/6i (palbociclib, abemaciclib, ribociclib) in both ESR1 wild-type and mutant backgrounds. Furthermore, we demonstrated that elacestrant, as a single agent and in combination, inhibited growth of patient-derived xenografts that have been derived from a patient previously treated with a CDK4/6i or exhibit de novo resistance to CDK4/6i. While the resistant lines demonstrate distinct alterations in cell cycle modulators, this did not affect elacestrant’s anti-tumor activity. In fact, we observe that elacestrant downregulates several key cell cycle players and halts cell cycle progression in vitro and in vivo. Conclusions We demonstrate that breast cancer tumor cells continue to rely on ER signaling to drive tumor growth despite exposure to CDK4/6i inhibitors. Importantly, elacestrant can inhibit this ER-dependent growth despite previously reported mechanisms of CDK4/6i resistance observed such as Rb loss, CDK6 overexpression, upregulated cyclinE1 and E2F1, among others. These data provide a scientific rationale for the evaluation of elacestrant in a post-CDK4/6i patient population. Additionally, elacestrant may also serve as an endocrine backbone for rational combinations to combat resistance.

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Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+ Metastasic Breast Cancer

Nanomaterials ◽

10.3390/nano9121793 ◽

2019 ◽

Vol 9 (12) ◽

pp. 1793 ◽

Cited By ~ 4

Author(s):

Enrique Niza ◽

María del Mar Noblejas-López ◽

Iván Bravo ◽

Cristina Nieto-Jiménez ◽

José Antonio Castro-Osma ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Therapeutic Potential ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Breast Cancer Cell Lines ◽

Her2 Positive ◽

Multikinase Inhibitor ◽

Biodegradable Nanoparticles

Dasatinib (DAS) is a multikinase inhibitor that acts on several signaling kinases. DAS is used as a second-line treatment for chronic accelerated myeloid and Philadelphia chromosome-positive acute lymphoblastic leukemia. The therapeutic potential of DAS in other solid tumours is under evaluation. As for many other compounds, an improvement in their pharmacokinetic and delivery properties would potential augment the efficacy. Antibody-targeted biodegradable nanoparticles can be useful in targeted cancer therapy. DAS has shown activity in human epidermal growth factor receptor 2 (HER2) positive tumors, so conjugation of this compound with the anti-HER2 antibody trastuzumab (TAB) with the use of nanocarriers could improve its efficacy. TAB-targeted DAS-loaded nanoparticles were generated by nanotechnology. The guided nanocarriers enhanced in vitro cytotoxicity of DAS against HER2 human breast cancer cell lines. Cellular mechanistic, release studies and nanoparticles stability were undertaken to provide evidences for positioning DAS-loaded TAB-targeted nanoparticles as a potential strategy for further development in HER2-overexpressing breast cancer therapy.

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Effects of suramin on cell-cycle kinetics of MCF-7 human breast cancer cells in vitro

British Journal of Cancer ◽

10.1038/bjc.1993.45 ◽

1993 ◽

Vol 67 (2) ◽

pp. 232-236 ◽

Cited By ~ 2

Author(s):

JA Foekens ◽

AM Sieuwerts ◽

EMJ Stuurman-Smeets ◽

HA Peters ◽

JGM Klijn

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Cell Cycle Kinetics ◽

Kinetics Of ◽

Mcf 7

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Interleukin-19 in Breast Cancer

Clinical and Developmental Immunology ◽

10.1155/2013/294320 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Ying-Yin Chen ◽

Chien-Feng Li ◽

Ching-Hua Yeh ◽

Ming-Shi Chang ◽

Chung-Hsi Hsing

Keyword(s):

Breast Cancer ◽

Therapeutic Potential ◽

Endotoxic Shock ◽

Tumor Stage ◽

Advanced Tumor Stage ◽

Duct Carcinoma ◽

Advanced Tumor ◽

And Migration

Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL-) 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored bothin vitroandin vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

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