scholarly journals Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ming-Xuan Feng ◽  
Jian-Xin Hong ◽  
Qiang Wang ◽  
Yong-Yong Fan ◽  
Chi-Ting Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Resorption ◽  
Molecular Mechanisms ◽  
Osteoclast Differentiation ◽  
Metastatic Breast ◽  
Osteoclast Formation ◽  
Migration And Invasion ◽  
Titanium Particle

Abstract Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients’ quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.

scholarly journals Biological Effects of β-Glucans on Osteoclastogenesis

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1982
Author(s):  
Wataru Ariyoshi ◽  
Shiika Hara ◽  
Ayaka Koga ◽  
Yoshie Nagai-Yoshioka ◽  
Ryota Yamasaki
Keyword(s):  
Bone Resorption ◽  
Bone Marrow Cells ◽  
Biological Effects ◽  
Osteoclast Differentiation ◽  
Treatment Strategies ◽  
Alcaligenes Faecalis ◽  
Osteoclast Formation ◽  
Osteoclast Precursors

Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker’s yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo. However, zymosan derived from S. cerevisiae stimulated the bone resorption activity and is widely used to induce arthritis in animal models. Additional research concerning the relationship between the molecular structure of β-glucan and its effect on osteoclastic bone resorption will be beneficial for the development of novel treatment strategies for bone-related diseases.

scholarly journals Saussurea lappaClarke-Derived Costunolide Prevents TNFα-Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF-κB Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Youn Kyung Choi ◽  
Sung-Gook Cho ◽  
Sang-Mi Woo ◽  
Yee Jin Yun ◽  
Jeakyung Jo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Breast Cancer Cell Growth

Saussurea lappaClarke (SLC) has been used as a traditional medicine in Korea, China, and Japan for the treatment of abdominal pain and tenesmus. Costunolide, a sesquiterpene lactone isolated from SLC, has diverse medicinal effects. However, the anticancer effects of costunolide are still unclear in breast cancer. In this study, we demonstrate that costunolide suppresses tumor growth and metastases of MDA-MB-231 highly metastatic human breast cancer cells via inhibiting TNFα-induced NF-κB activation. Costunolide inhibited MDA-MB-231 tumor growth and metastases without affecting body weights in thein vivomouse orthotopic tumor growth assays. In addition, costunolide inhibitedin vitroTNFα-induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNFα-induced NF-κB signaling activation, resulting in a reduced expression of MMP-9, a well-known NF-κB-dependent gene to mediate breast cancer cell growth and metastases. Therefore, we conclude that SLC and its derivative costunolide suppress breast cancer growth and metastases by inhibiting TNFα-induced NF-κB activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer.

scholarly journals CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Fang Wang ◽  
Xiaochun Wang ◽  
Jingruo Li ◽  
Pengwei Lv ◽  
Mingli Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cytokine Signaling

Abstract Background Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). Materials and methods qRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10. Results CircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10. Conclusions CircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.

scholarly journals Vindoline Attenuates Osteoarthritis Progression Through Suppressing the NF-κB and ERK Pathways in Both Chondrocytes and Subchondral Osteoclasts

2022 ◽  
Vol 12 ◽  
Author(s):  
Meisong Zhu ◽  
Qiang Xu ◽  
Xinmin Yang ◽  
Haibo Zhan ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Osteoclast Differentiation ◽  
Indole Alkaloid ◽  
Protective Role ◽  
Osteoclast Formation ◽  
Dependent Manner ◽  
Osteoarthritis Progression ◽  
Anti Inflammatory

Disruption of extracellular matrix (ECM) homeostasis and subchondral bone remodeling play significant roles in osteoarthritis (OA) pathogenesis. Vindoline (Vin), an indole alkaloid extracted from the medicinal plant Catharanthus roseus, possesses anti-inflammatory properties. According to previous studies, inflammation is closely associated with osteoclast differentiation and the disorders of the homeostasis between ECM. Although Vin has demonstrated effective anti-inflammatory properties, its effects on the progression of OA remain unclear. We hypothesized that Vin may suppress the progress of OA by suppressing osteoclastogenesis and stabilizing ECM of articular cartilage. Therefore, we investigated the effects and molecular mechanisms of Vin as a treatment for OA in vitro and in vivo. In the present study, we found that Vin significantly suppressed RANKL-induced osteoclast formation and obviously stabilized the disorders of the ECM homeostasis stimulated by IL-1β in a dose-dependent manner. The mRNA expressions of osteoclast-specific genes were inhibited by Vin treatment. Vin also suppressed IL-1β-induced mRNA expressions of catabolism and protected the mRNA expressions of anabolism. Moreover, Vin notably inhibited the activation of RANKL-induced and IL-1β-induced NF-κB and ERK pathways. In vivo, Vin played a protective role by inhibiting osteoclast formation and stabilizing cartilage ECM in destabilization of the medial meniscus (DMM)-induced OA mice. Collectively, our observations provide a molecular-level basis for Vin’s potential in the treatment of OA.

scholarly journals MnTnHex-2-PyP5+, Coupled to Radiation, Suppresses Metastasis of 4T1 and MDA-MB-231 Breast Cancer via AKT/Snail/EMT Pathways

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1769
Author(s):  
Sung-Won Shin ◽  
Changhoon Choi ◽  
Hakyoung Kim ◽  
Yeeun Kim ◽  
Sohee Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Tumor Growth Inhibition ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
4T1 Cells

Tumor migration and invasion induced by the epithelial-to-mesenchymal transition (EMT) are prerequisites for metastasis. Here, we investigated the inhibitory effect of a mimic of superoxide dismutase (SOD), cationic Mn(III) ortho-substituted N-n-hexylpyridylporphyrin (MnTnHex-2-PyP5+, MnHex) on the metastasis of breast cancer in cellular and animal models, focusing on the migration of tumor cells and the factors that modulate this behavior. Wound healing and Transwell migration assays revealed that the migration of mouse mammary carcinoma 4T1 cells was markedly reduced during the concurrent treatment of MnHex and radiation therapy (RT) compared with that of the control and RT alone. Bioluminescence imaging showed that MnHex/RT co-treatment dramatically reduced lung metastasis of 4T1 cells in mice, compared with the sham control and both single treatments. Western blotting and immunofluorescence showed that MnHex treatment of 4T1 cells reversed the RT-induced EMT via inhibiting AKT/GSK-3β/Snail pathway in vitro, thereby decreasing cell migration and invasion. Consistently, histopathological analyses of 4T1 tumors showed that MnHex/RT reduced Snail expression, blocked EMT, and in turn suppressed metastases. Again, in the human metastatic breast cancer MDA-MB-231 cell line, MnHex inhibited metastatic potential in vitro and in vivo and suppressed the RT-induced Snail expression. In addition to our previous studies showing tumor growth inhibition, this study demonstrated that MnHex carries the ability to minimize the metastatic potential of RT-treated cancers, thus overcoming their radioresistance.

scholarly journals F1012-2 Induced ROS-Mediated DNA Damage Response through Activation of MAPK Pathway in Triple-Negative Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Lingjie Dai ◽  
Shasha Tian ◽  
Jinyao Zhang ◽  
Mengyuan Lu ◽  
Jingchao Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Migration And Invasion

We have previously reported that F1012-2, a sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC., exhibits strong effects against Triple Negative Breast Cancer (TNBC). In this study, we found F1012-2 effectively inhibited cell migration and invasion detected by wound healing and transwell assays. In order to elucidate the potential mechanisms of F1012-2, we further studied its effect on DNA damage in TNBC cell lines. Using single cell gel electrophoresis (comet assay), immunofluorescence, and western blotting assays, we found that F1012-2 treatment induced significant DNA strand breaks and γ-H2AX activation. Moreover, exposure to F1012-2 led to overproduction of reactive oxygen species (ROS). NAC treatment completely eliminated ROS, which may be due to the interaction between NAC and F1012-2. A further study of the molecular mechanisms demonstrated that the MAPK signaling pathway participated in the anti-TNBC effect of F1012-2. Pretreatment with specific inhibitors targeting JNK (SP600125) and ERK (PD98059) could rescue the decrease in cell viability and inhibit expressions of JNK and ERK phosphorylation, but SB203580 had no effects. Finally, in the acute toxicity experiment, there were no obvious symptoms of poisoning in the F1012-2 treatment group. An in vivo study demonstrated that F1012-2 significantly suppressed the tumor growth and induced DNA damage. In conclusion, the activity of F1012-2-induced DNA damage in TNBC was found in vivo and in vitro, which might trigger the MAPK pathway through ROS accumulation. These results indicate that F1012-2 may be an effective anti-TNBC therapeutic agent.

scholarly journals Jatrorrhizine Hydrochloride Suppresses RANKL-Induced Osteoclastogenesis and Protects against Wear Particle-Induced Osteolysis

2018 ◽  
Vol 19 (11) ◽  
pp. 3698 ◽  
Author(s):  
Hui Li ◽  
Jing Wang ◽  
Qiwen Sun ◽  
Gang Chen ◽  
Shengnan Sun ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Chinese Herb ◽  
Major Complication ◽  
Wear Particle ◽  
Osteoclast Formation ◽  
Marker Genes

Wear particle-induced aseptic prosthetic loosening is a major complication associated with total joint arthroplasty (TJA). A growing body of evidence suggests that receptor activator of nuclear factor κ-B ligand (RANKL)-stimulated osteoclastogenesis and bone resorption are responsible for peri-implant loosening. Thus, agents which attenuate excessive osteoclast differentiation and function have been considered to offer therapeutic potential for prolonging the life of TJA implants. Jatrorrhizine hydrochloride (JH), a major protoberberine alkaloid isolated from the traditional Chinese herb Coptis chinensis, has been reported to have antimicrobial, antitumor, and antihypercholesterolemic and neuroprotective activities. However, its effects on osteoclast biology remain unknown. Here, we found that JH inhibited RANKL-induced osteoclast formation and bone resorption in vitro and exerted protection against titanium (Ti) particle-induced osteolysis in vivo. Biochemical analysis demonstrated that JH suppressed RANKL-induced activation of MAPKs (p38 and ERK) which down-regulated the production of NFATc1 and NFATc1-regulated osteoclastic marker genes, such as TRAP, CTR and CTSK. Collectively, our findings suggest that JH may be a promising anti-osteoclastogenesis agent for treating periprosthetic osteolysis or other osteoclast-related osteolytic diseases.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

scholarly journals Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1366
Author(s):  
Russell Hughes ◽  
Xinyue Chen ◽  
Natasha Cowley ◽  
Penelope D. Ottewell ◽  
Rhoda J. Hawkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Accessory Cell ◽  
Cancer Cell Survival

Metastatic breast cancer in bone is incurable and there is an urgent need to develop new therapeutic approaches to improve survival. Key to this is understanding the mechanisms governing cancer cell survival and growth in bone, which involves interplay between malignant and accessory cell types. Here, we performed a cellular and molecular comparison of the bone microenvironment in mouse models representing either metastatic indolence or growth, to identify mechanisms regulating cancer cell survival and fate. In vivo, we show that regardless of their fate, breast cancer cells in bone occupy niches rich in osteoblastic cells. As the number of osteoblasts in bone declines, so does the ability to sustain large numbers of breast cancer cells and support metastatic outgrowth. In vitro, osteoblasts protected breast cancer cells from death induced by cell stress and signaling via gap junctions was found to provide important juxtacrine protective mechanisms between osteoblasts and both MDA-MB-231 (TNBC) and MCF7 (ER+) breast cancer cells. Combined with mathematical modelling, these findings indicate that the fate of DTCs is not controlled through the association with specific vessel subtypes. Instead, numbers of osteoblasts dictate availability of protective niches which breast cancer cells can colonize prior to stimulation of metastatic outgrowth.

scholarly journals Potential Role of microRNA-183 as a Tumor Suppressor in Hepatocellular Carcinoma

2018 ◽  
Vol 51 (5) ◽  
pp. 2065-2072 ◽  
Author(s):  
Wei Bian ◽  
Hongfei Zhang ◽  
Miao Tang ◽  
Shaojun Zhang ◽  
Lichao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Reporter Assays

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

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