scholarly journals Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zizheng Zou ◽  
Xiyuan Hu ◽  
Tiao Luo ◽  
Zhengnan Ming ◽  
Xiaodan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Down Regulation ◽  
Pyrimidine Synthesis ◽  
Naturally Occurring ◽  
Argininosuccinate Synthase ◽  
Tumor Inhibitor ◽  
Therapeutic Avenue

AbstractArgininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1.

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

scholarly journals The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricardo Romero-Moreno ◽  
Kimberly J. Curtis ◽  
Thomas R. Coughlin ◽  
Maria Cristina Miranda-Vergara ◽  
Shourik Dutta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ex Vivo ◽  
Metastatic Cancer ◽  
Culture Method ◽  
Cancer Cell Proliferation ◽  
Promote Breast Cancer

Abstract Bone is one of the most common sites for metastasis across cancers. Cancer cells that travel through the vasculature and invade new tissues can remain in a non-proliferative dormant state for years before colonizing the metastatic site. Switching from dormancy to colonization is the rate-limiting step of bone metastasis. Here we develop an ex vivo co-culture method to grow cancer cells in mouse bones to assess cancer cell proliferation using healthy or cancer-primed bones. Profiling soluble factors from conditioned media identifies the chemokine CXCL5 as a candidate to induce metastatic colonization. Additional studies using CXCL5 recombinant protein suggest that CXCL5 is sufficient to promote breast cancer cell proliferation and colonization in bone, while inhibition of its receptor CXCR2 with an antagonist blocks proliferation of metastatic cancer cells. This study suggests that CXCL5 and CXCR2 inhibitors may have efficacy in treating metastatic bone tumors dependent on the CXCL5/CXCR2 axis.

scholarly journals Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Travis B. Salisbury ◽  
Gary Z. Morris ◽  
Justin K. Tomblin ◽  
Ateeq R. Chaudhry ◽  
Carla R. Cook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Aryl Hydrocarbon

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P<0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity.

Down regulation of CSL activity inhibits cell proliferation in prostate and breast cancer cells

2011 ◽  
Vol 112 (9) ◽  
pp. 2340-2351 ◽  
Author(s):  
Thomas Yong ◽  
Amanda Sun ◽  
Michael D. Henry ◽  
Shari Meyers ◽  
J. Nathan Davis
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Down Regulation

scholarly journals Alternative MyD88 -Cyclin D1 signaling in breast cancer cells regulates TLR3 mediated cell proliferation

2020 ◽  
Author(s):  
Aradhana Singh ◽  
Ranjitsinh Devkar ◽  
Anupam Basu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Adjuvant Therapy ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Surface Localization ◽  
Tlr3 Signaling

AbstractTLR3 mediated apoptotic changes in cancer cells are well documented and hence several synthetic ligands of TLR3 are being used for adjuvant therapy. But there are reports showing contradictory effect of TLR3 signaling which includes our previous report that had shown cell proliferation following surface localization of TLR 3. However, the underlying mechanism of cell surface localization of TLR3 and subsequent cell proliferation lacks clarity. This study addresses TLR3 ligand mediated signaling cascade that regulates a proliferative effect in breast cancer cells (MDA MB 231 and T47D) challenged with TLR3 ligand in the presence of MyD88 inhibitor. Evidences were obtained using immunoblotting, co-immunoprecipitation, confocal microscopy, Immunocytochemistry, ELISA, and flowcytometry. Results had revealed that TLR3 ligand treatment significantly enhanced breast cancer cell proliferation marked by an upregulated expression of cyclinD1 but the same were suppressed by addition of MyD88 inhibitor. Also, expression of IRAK1-TRAF6-TAK1 were altered in the given TLR3-signaling pathway. Inhibition of MyD88 disrupted the downstream adaptor complex and mediated signaling through TLR3-MyD88-NF-κB (p65)-IL6-Cyclin D1 pathway. TLR3 mediated alternative signaling of the TLR3-MyD88-IRAK1-TRAF6-TAK1-TAB1-NF-κB axis leads to upregulation of IL6 and cyclinD1. This response is hypothesized to be via the MyD88 gateway that culminates in proliferation of breast cancer cells. Overall, this study provides first comprehensive evidence on involvement of canonical signaling of TLR3 using MyD88 - Cyclin D1 mediated breast cancer cell proliferation. The findings elucidated herein will provide valuable insights into understand the TLR3 mediated adjuvant therapy in cancer.

scholarly journals Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation

2020 ◽  
Vol 21 (8) ◽  
pp. 2906
Author(s):  
Yih Ho ◽  
Zi-Lin Li ◽  
Ya-Jung Shih ◽  
Yi-Ru Chen ◽  
Kuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Plasma Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Integrin Αvβ3 ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation

Hormones and their receptors play an important role in the development and progression of breast cancer. Hormones regulate the proliferation of breast cancer cells through binding between estrogen or progestins and steroid receptors that may reside in the cytoplasm or be transcriptionally activated as steroid–protein nuclear receptor complexes. However, receptors for nonpeptide hormones also exist in the plasma membrane. Via those receptors, hormones are able to stimulate breast cancer cell proliferation when activated. Integrins are heterodimeric structural proteins of the plasma membrane. Their primary functions are to interact with extracellular matrix proteins and growth factors. Recently, integrin αvβ3 has been identified as a receptor for nonpeptide hormones, such as thyroid hormone and dihydrotestosterone (DHT). DHT promotes the proliferation of human breast cancer cells through binding to integrin αvβ3. A receptor for resveratrol, a polyphenol stilbene, also exists on this integrin in breast cancer cells, mediating the anti-proliferative, pro-apoptotic action of the compound in these cells. Unrelated activities of DHT and resveratrol that originate at integrin depend upon downstream stimulation of mitogen-activated protein kinase (MAPK, ERK1/2) activity, suggesting the existence of distinct, function-specific pools of ERK1/2 within the cell. This review will discuss the features of these receptors in breast cancer cells, in turn suggesting clinical applications that are based on the interactions of resveratrol/DHT with integrin αvβ3 and other androgen receptors.

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