S-Adenosylmethionine Inhibits Cell Growth and Migration of Triple Negative Breast Cancer Cells through Upregulating MiRNA-34c and MiRNA-449a

Triple-negative breast cancer (TNBC) is one of the most common malignancies worldwide and shows maximum invasiveness and a high risk of metastasis. Recently, many natural compounds have been highlighted as a valuable source of new and less toxic drugs to enhance breast cancer therapy. Among them, S-adenosyl-L-methionine (AdoMet) has emerged as a promising anti-cancer agent. MicroRNA (miRNA or miR)-based gene therapy provides an interesting antitumor approach to integrated cancer therapy. In this study, we evaluated AdoMet-induced modulation of miRNA-34c and miRNA-449a expression in MDA-MB-231 and MDA-MB-468 TNBC cells. We demonstrated that AdoMet upregulates miR-34c and miR-449a expression in both cell lines. We found that the combination of AdoMet with miR-34c or miR-449a mimic strongly potentiated the pro-apoptotic effect of the sulfonium compound by a caspase-dependent mechanism. For the first time, by video time-lapse microscopy, we showed that AdoMet inhibited the in vitro migration of MDA-MB-231 and MDA-MB-468 cells and that the combination with miR-34c or miR-449a mimic strengthened the effect of the sulfonium compound through the modulation of β-catenin and Small Mother Against Decapentaplegic (SMAD) signaling pathways. Our results furnished the first evidence that AdoMet exerts its antitumor effects in TNBC cells through upregulating the expression of miR-34c and miR-449a.

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LINC01234 aggravates cell growth and migration of triple‐negative breast cancer by activating the Wnt pathway

Environmental Toxicology ◽

10.1002/tox.23318 ◽

2021 ◽

Author(s):

Feng Xiao ◽

Hongyao Jia ◽

Di Wu ◽

Zhiru Zhang ◽

Sijie Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Triple Negative Breast Cancer ◽

Wnt Pathway ◽

Triple Negative ◽

Cell Growth And Migration ◽

And Migration

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Rad51 Silencing with siRNA Delivered by Porous Silicon-Based Microparticle Enhances the Anti-Cancer Effect of Doxorubicin in Triple-Negative Breast Cancer

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3198 ◽

2021 ◽

Vol 17 (12) ◽

pp. 2351-2363

Author(s):

Zeliang Wu ◽

Lin Zhu ◽

Junhua Mai ◽

Haifa Shen ◽

Rong Xu

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Porous Silicon ◽

Lung Metastasis ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Antitumor Effects ◽

Mesenchymal Transition ◽

Tnbc Cell

Due to its high heterogeneity and aggressiveness, cytotoxic chemotherapy is still a mainstay treatment for triple negative breast cancer. Unfortunately, the above mentioned has not significantly ameliorated TNBC patients and induces drug resistance. Exploring the mechanisms underlying the chemotherapy sensitivity of TNBC and developing novel sensitization strategies are promising approaches for improving the prognosis of patients. Rad51, a key regulator of DNA damage response pathway, repairs DNA damage caused by genotoxic agents through “homologous recombination repair.” Therefore, Rad51 inhibition may increase TNBC cell sensitivity to anticancer agents. Based on these findings, we first designed Rad51 siRNA to inhibit the Rad51 protein expression in vitro and evaluated the sensitivity of TNBC cells to doxorubicin. Subsequently, we constructed discoidal porous silicon microparticles (pSi) and encapsulated discoidal 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes/siRad51 (PS-DOPC/siRad51) to explore the synergistic antitumor effects of siRad51 and doxorubicin on two mouse models of TNBC in vivo. Our in vitro studies indicated that siRad51 enhanced the efficacy of DOX chemotherapy and significantly suppressed TNBC cell proliferation and metastasis. This effect was related to apoptosis induction and epithelial to mesenchymal transition (EMT) inhibition. siRad51 altered the expression of apoptosis- and EMT-related proteins. In orthotopic and lung metastasis xenograft models, the administration of PS-DOPC/siRad51 in combination with DOX significantly alleviated the primary tumor burden and lung metastasis, respectively. Our current studies present an efficient strategy to surmount chemotherapy resistance in TNBC through microvector delivery of siRad51.

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Synergistic antitumor effects of S-1 with eribulin in vitro and in vivo for triple-negative breast cancer cell lines

SpringerPlus ◽

10.1186/2193-1801-3-417 ◽

2014 ◽

Vol 3 (1) ◽

pp. 417 ◽

Cited By ~ 15

Author(s):

Masato Terashima ◽

Kazuko Sakai ◽

Yosuke Togashi ◽

Hidetoshi Hayashi ◽

Marco A De Velasco ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Cell Lines ◽

Antitumor Effects

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Nanoparticles Loaded with the BET Inhibitor JQ1 Block the Growth of Triple Negative Breast Cancer Cells In Vitro and In Vivo

Cancers ◽

10.3390/cancers12010091 ◽

2019 ◽

Vol 12 (1) ◽

pp. 91 ◽

Cited By ~ 2

Author(s):

Valentina Maggisano ◽

Marilena Celano ◽

Rocco Malivindi ◽

Ines Barone ◽

Donato Cosco ◽

...

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Anticancer Efficacy ◽

Bet Inhibitor ◽

Physico Chemical ◽

And Migration

Inhibition of bromo-and extra-terminal domain (BET) proteins, epigenetic regulators of genes involved in cell viability, has been efficiently tested in preclinical models of triple negative breast cancer (TNBC). However, the use of the selective BET-inhibitor JQ1 on humans is limited by its very short half-life. Herein, we developed, characterized and tested a novel formulation of nanoparticles containing JQ1 (N-JQ1) against TNBC in vitro and in vivo. N-JQ1, prepared using the nanoprecipitation method of preformedpoly-lactid-co-glycolic acid in an aqueous solution containing JQ1 and poloxamer-188 as a stabilizer, presented a high physico-chemical stability. Treatment of MDA-MB 157 and MDA-MB 231 TNBC cells with N-JQ1 determined a significant decrease in cell viability, adhesion and migration. Intra-peritoneal administration (5 days/week for two weeks) of N-JQ1 in nude mice hosting a xenograft TNBC after flank injection of MDA-MB-231 cells determined a great reduction in the growth and vascularity of the neoplasm. Moreover, the treatment resulted in a minimal infiltration of nearby tissues. Finally, the encapsulation of JQ1 in nanoparticles improved the anticancer efficacy of this epigenetic compound against TNBC in vitro and in vivo, opening the way to test it in the treatment of TNBC.

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Adjuvant Melatonin Analogs Could Be Beneficial in Triple Negative Breast Cancer Therapy In Vitro

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2019.10.206 ◽

2019 ◽

Vol 145 ◽

pp. S78

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Therapy

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ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer

10.21203/rs.3.rs-34444/v2 ◽

2020 ◽

Author(s):

Yu-Chen Cai ◽

Hang Yang ◽

Ke-Feng Wang ◽

Tan-Huan Chen ◽

Wen-Qi Jiang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Migration And Invasion ◽

Tumor Cell Adhesion ◽

Tumor Tissues ◽

Cell Adhesion And Migration ◽

And Migration

Abstract Background: Triple-negative breast cancer (TNBC) patients have relatively poor clinical outcomes. A marker predicting the prognosis of patients with TNBC could help guide treatment. Extensive evidence demonstrates that angiopoietin-like 4 (ANGPTL4) is involved in the regulation of cancer growth, metastasis and angiogenesis. Therefore, its role in TNBC is of interest.Methods: We tested the ANGPTL4 expression level in tumor tissues by immunohistochemistry (IHC) and detected its association with the clinical features of TNBC patients. Next, the effects and mechanisms of ANGPTL4 on TNBC cell migration and adhesion were investigated.Results: We found that ANGPTL4 overexpression was associated with favorable outcomes in TNBC patients. ANGPTL4 upregulation inhibited cell adhesion, migration and invasion in vitro. Further analyses demonstrated that the possible mechanism might involve suppression of TNBC progression by interacting with extracellular matrix-related genes.Conclusions: The present findings demonstrated that enhancement of ANGPTL4 expression might inversely correlate with TNBC progression. ANGPTL4 is a promising marker of TNBC and should be evaluated in further studies. Trial registration: Retrospectively registered.

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ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer

10.21203/rs.3.rs-34444/v3 ◽

2020 ◽

Author(s):

Yu-Chen Cai ◽

Hang Yang ◽

Ke-Feng Wang ◽

Tan-Huan Chen ◽

Wen-Qi Jiang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Migration And Invasion ◽

Tumor Cell Adhesion ◽

Tumor Tissues ◽

Cell Adhesion And Migration ◽

And Migration

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ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer

BMC Cancer ◽

10.1186/s12885-020-07343-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yu-Chen Cai ◽

Hang Yang ◽

Ke-Feng Wang ◽

Tan-Huan Chen ◽

Wen-Qi Jiang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Migration And Invasion ◽

Tumor Cell Adhesion ◽

Tumor Tissues ◽

Cell Adhesion And Migration ◽

And Migration

Abstract Background Triple-negative breast cancer (TNBC) patients have relatively poor clinical outcomes. A marker predicting the prognosis of patients with TNBC could help guide treatment. Extensive evidence demonstrates that angiopoietin-like 4 (ANGPTL4) is involved in the regulation of cancer growth, metastasis and angiogenesis. Therefore, its role in TNBC is of interest. Methods: We tested the ANGPTL4 expression level in tumor tissues by immunohistochemistry (IHC) and detected its association with the clinical features of TNBC patients. Next, the effects and mechanisms of ANGPTL4 on TNBC cell migration and adhesion were investigated. Results We found that ANGPTL4 overexpression was associated with favorable outcomes in TNBC patients. ANGPTL4 upregulation inhibited cell adhesion, migration and invasion in vitro. Further analyses demonstrated that the possible mechanism might involve suppression of TNBC progression by interacting with extracellular matrix-related genes. Conclusions The present findings demonstrated that enhancement of ANGPTL4 expression might inversely correlate with TNBC progression. ANGPTL4 is a promising marker of TNBC and should be evaluated in further studies. Trial registration Retrospectively registered.

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Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal transition of triple negative breast cancer cells via HDAC8/FOXA1 signals

Biological Chemistry ◽

10.1515/hsz-2015-0215 ◽

2016 ◽

Vol 397 (1) ◽

pp. 75-83 ◽

Cited By ~ 24

Author(s):

Shao Wu ◽

Zhi Luo ◽

Peng-Jiu Yu ◽

Hui Xie ◽

Yu-Wen He

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Histone Deacetylases ◽

Hydroxamic Acid ◽

Triple Negative ◽

Nuclear Translocation ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Cancer Agent

Abstract Inhibitor of histone deacetylases (HDACIs) have great therapeutic value for triple negative breast cancer (TNBC) patients. Interestingly, our present study reveals that suberoyl anilide hydroxamic acid (SAHA), one of the most advanced pan-HDAC inhibitor, can obviously promote in vitro motility of MDA-MB-231 and BT-549 cells via induction of epithelial-mesenchymal transition (EMT). SAHA treatment significantly down-regulates the expression of epithelial markers E-cadherin (E-Cad) while up-regulates the mesenchymal markers N-cadherin (N-Cad), vimentin (Vim) and fibronectin (FN). However, SAHA has no effect on the expression and nuclear translocation of EMT related transcription factors including Snail, Slug, Twist and ZEB. While SAHA treatment down-regulates the protein and mRNA expression of FOXA1 and then decreases its nuclear translocation. Over-expression of FOXA1 markedly attenuates SAHA induced EMT of TNBC cells. Further, silence of HDAC8, while not HDAC6, alleviates the down-regulation of FOXA1 and up-regulation of N-Cad and Vim in MDA-MB-231 cells treated with SAHA. Collectively, our present study reveals that SAHA can promote EMT of TNBC cells via HDAC8/FOXA1 signals, which suggests that more attention should be paid when SAHA is used as anti-cancer agent for cancer treatment.

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