Tea Polyphenol Epigallocatechin-3-Gallate Inhibits Cell Proliferation In a Patient-Derived Triple-Negative Breast Cancer Xenograft Mouse Model Via Inhibition of Proline-Dehydrogenase-Induced Effects

The interest in palladium(II) compounds as potential new anticancer drugs has increased in recent years, due to their high toxicity and acquired resistance to platinum(II)-derived agents, namely cisplatin. In fact, palladium complexes with biogenic polyamines (e.g., spermine, Pd2Spm) have been known to display favorable antineoplastic properties against distinct human breast cancer cell lines. This study describes the in vivo response of triple-negative breast cancer (TNBC) tumors to the Pd2Spm complex or to cisplatin (reference drug), compared to tumors in vehicle-treated mice. Both polar and lipophilic extracts of tumors, excised from a MDA-MB-231 cell-derived xenograft mouse model, were characterized through nuclear magnetic resonance (NMR) metabolomics. Interestingly, the results show that polar and lipophilic metabolomes clearly exhibit distinct responses for each drug, with polar metabolites showing a stronger impact of the Pd(II)-complex compared to cisplatin, whereas neither drug was observed to significantly affect tumor lipophilic metabolism. Compared to cisplatin, exposure to Pd2Spm triggered a higher number of, and more marked, variations in some amino acids, nucleotides and derivatives, membrane precursors (choline and phosphoethanolamine), dimethylamine, fumarate and guanidine acetate, a signature that may be relatable to the cytotoxicity and/or mechanism of action of the palladium complex. Putative explanatory biochemical hypotheses are advanced on the role of the new Pd2Spm complex in TNBC metabolism.

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Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽

10.1007/s12282-021-01221-4 ◽

2021 ◽

Author(s):

Yingzi Zhang ◽

Jiao Tian ◽

Chi Qu ◽

Yang Peng ◽

Jinwei Lei ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Cell Counting ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

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Potential of three-step pretargeting radioimmunotherapy using biotinylated bevacizumab and succinylated streptavidin in triple-negative breast cancer xenograft

Annals of Nuclear Medicine ◽

10.1007/s12149-021-01597-5 ◽

2021 ◽

Author(s):

Wenchao Gu ◽

Ryan Yudistiro ◽

Hirofumi Hanaoka ◽

Natsumi Katsumata ◽

Yoshito Tsushima

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Xenograft

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LncRNA DLX6-AS1 Contributes to Epithelial–Mesenchymal Transition and Cisplatin Resistance in Triple-negative Breast Cancer via Modulating Mir-199b-5p/Paxillin Axis

Cell Transplantation ◽

10.1177/0963689720929983 ◽

2020 ◽

Vol 29 ◽

pp. 096368972092998 ◽

Cited By ~ 1

Author(s):

Chuang Du ◽

Yan Wang ◽

Yingying Zhang ◽

Jianhua Zhang ◽

Linfeng Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Drug Resistance ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cisplatin Resistance ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Expression Levels

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer types with high recurrence, metastasis, and drug resistance. Recent studies report that long noncoding RNAs (lncRNAs)-mediated competing endogenous RNAs (ceRNA) play an important role in tumorigenesis and drug resistance of TNBC. Although elevated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) has been observed to promote carcinogenesis in various cancers, the role in TNBC remained unclear. In this study, expression levels of DLX6-AS1 were increased in TNBC tissues and cell lines when compared with normal tissues or breast fibroblast cells which were determined by quantitative real-time PCR (RT-qPCR). Then, CCK-8 assay, cell colony formation assay and western blot were performed in CAL-51 cells transfected with siRNAs of DLX6-AS1 or MDA-MB-231 cells transfected with DLX6-AS1 over expression plasmids. Knock down of DLX6-AS1 inhibited cell proliferation, epithelial-mesenchymal transition (EMT), decreased expression levels of BCL2 apoptosis regulator (Bcl-2), Snail family transcriptional repressor 1 (Snail) as well as N-cadherin and decreased expression levels of cleaved caspase-3, γ-catenin as well as E-cadherin, while up regulation of DLX6-AS1 had the opposite effect. Besides, knockdown of DLX6-AS1 in CAL-51 cells or up regulation of DLX6-AS1 in MDA-MB-231 cells also decreased or increased cisplatin resistance of those cells analyzed by MTT assay. Moreover, by using dual luciferase reporter assay, RNA immunoprecipitation and RNA pull down assay, a ceRNA which was consisted by lncRNA DLX6-AS1, microRNA-199b-5p (miR-199b-5p) and paxillin (PXN) was identified. And DLX6-AS1 function through miR-199b-5p/PXN in TNBC cells. Finally, results of xenograft experiments using nude mice showed that DLX6-AS1 regulated cell proliferation, EMT and cisplatin resistance by miR-199b-5p/PXN axis in vivo. In brief, DLX6-AS1 promoted cell proliferation, EMT, and cisplatin resistance through miR-199b-5p/PXN signaling in TNBC in vitro and in vivo.

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Tobacco mosaic virus delivery of mitoxantrone for cancer therapy

Nanoscale ◽

10.1039/c8nr04142c ◽

2018 ◽

Vol 10 (34) ◽

pp. 16307-16313 ◽

Cited By ~ 6

Author(s):

Richard D. Lin ◽

Nicole F. Steinmetz

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Mouse Model ◽

Tobacco Mosaic Virus ◽

Mosaic Virus ◽

Triple Negative Breast Cancer ◽

Topoisomerase Ii ◽

Triple Negative ◽

Topoisomerase Ii Inhibitor ◽

Virus Delivery

Tobacco mosaic virus-nanoparticle encapsulation of the topoisomerase II inhibitor mitoxantrone enables therapy in a mouse model of triple negative breast cancer.

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