scholarly journals Aurantoside C Targets and Induces Apoptosis in Triple Negative Breast Cancer Cells

Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 361 ◽  
Author(s):  
Sumi Shrestha ◽  
Anabel Sorolla ◽  
Jane Fromont ◽  
Pilar Blancafort ◽  
Gavin Flematti
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Triple Negative ◽  
Cytotoxic Activities ◽  
Chemotherapeutic Drugs ◽  
Breast Cancers ◽  
Cyclin E1

Triple negative breast cancer (TNBC) is a subtype of breast cancers that currently lacks effective targeted therapy. In this study, we found that aurantoside C (C828), isolated from the marine sponge Manihinea lynbeazleyae collected from Western Australia, exhibited higher cytotoxic activities in TNBC cells compared with non-TNBC (luminal and normal-like) cells. The cytotoxic effect of C828 was associated to the accumulation of cell at S-phase, resulting in the decline of cyclin D1, cyclin E1, CDK4, and CDK6, and an increase in p21. We also found that C828 inhibited the phosphorylation of Akt/mTOR and NF-kB pathways and increased the phosphorylation of p38 MAPK and SAPK/JNK pathways, leading to apoptosis in TNBC cells. These effects of C828 were not observed in non-TNBC cells at the concentrations that were cytotoxic to TNBC cells. When compared to the cytotoxic effect with the chemotherapeutic drugs doxorubicin and cisplatin, C828 was found to be 20 times and 35 times more potent than doxorubicin and cisplatin, respectively. These results indicate that C828 could be a promising lead for developing new anticancer agents that target TNBC cells.

scholarly journals Design, synthesis, and biological evaluation of new 6,N2-diaryl-1,3,5-triazine-2,4-diamines as anticancer agents selectively targeting triple negative breast cancer cells

RSC Advances ◽  
2020 ◽  
Vol 10 (43) ◽  
pp. 25517-25528
Author(s):  
Ahmad Junaid ◽  
Felicia Phei Lin Lim ◽  
Edward R. T. Tiekink ◽  
Anton V. Dolzhenko
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
3D Qsar ◽  
Qsar Model ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation

New highly potent and selective 6,N2-diaryl-1,3,5-triazine-2,4-diamines were designed and prepared using the 3D-QSAR model developed earlier.

scholarly journals Knockdown of A-kinase anchor protein 4 inhibits proliferation of triple-negative breast cancer cells in vitro and in vivo

Tumor Biology ◽  
2020 ◽  
Vol 42 (4) ◽  
pp. 101042832091447 ◽  
Author(s):  
Nirmala Jagadish ◽  
Sonika Devi ◽  
Namita Gupta ◽  
Vitusha Suri ◽  
Anil Suri
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Anchor Protein

Triple-negative breast cancers are the most aggressive subtypes with poor prognosis due to lack of targeted cancer therapy. Recently, we reported an association of A-kinase anchor protein 4 expression with various clinico-pathological parameters of breast cancer patients. In this context, we examined the effect of knockdown of A-kinase anchor protein 4 on cell cycle, apoptosis, cellular proliferation, colony formation, migration, and invasion in triple-negative breast cancer cells. We also examined the synergistic cytotoxic effect of paclitaxel on A-kinase anchor protein 4 downregulated triple-negative breast cancer cells. Knockdown of A-kinase anchor protein 4 resulted in significant reduction in cellular growth and migratory abilities. Interestingly, we also observed enhanced cell death in A-kinase anchor protein 4 downregulated cells treated with paclitaxel. Knockdown of A-kinase anchor protein 4 in cell cycle resulted in G0/G1 phase arrest. Knockdown of A-kinase anchor protein 4 also led to increased reactive oxygen species generation as a result of upregulation of NOXA and CHOP. In addition, levels of cyclins, cyclin-dependent kinases, anti-apoptotic molecules, and mesenchymal markers were reduced in A-kinase anchor protein 4 downregulated cells. Moreover, downregulation of A-kinase anchor protein 4 also caused tumor growth reduction in in vivo studies. These data together suggest that A-kinase anchor protein 4 downregulation inhibits various malignant properties and enhances the cytotoxic effect of paclitaxel, and this combinatorial approach could be useful for triple-negative breast cancer treatment.

scholarly journals Anthocyanidins Inhibit Growth and Chemosensitize Triple-Negative Breast Cancer via the NF-κB Signaling Pathway

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6248
Author(s):  
Farrukh Aqil ◽  
Radha Munagala ◽  
Ashish K. Agrawal ◽  
Jeyaprakash Jeyabalan ◽  
Neha Tyagi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Triple Negative Breast Cancer ◽  
Tumor Volume ◽  
Triple Negative ◽  
Control Treatment ◽  
Chemotherapeutic Drugs ◽  
Breast Cancers ◽  
Development Of Resistance ◽  
Metastatic Relapse

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is the only systemic treatment option. Although chemotherapeutic drugs respond initially in TNBC, many patients relapse and have a poor prognosis. Poor survival after metastatic relapse is largely attributed to the development of resistance to chemotherapeutic drugs. In this study, we show that bilberry-derived anthocyanidins (Anthos) can inhibit the growth and metastasis of TNBC and chemosensitize paclitaxel (PAC)-resistant TNBC cells by modulating the NF-κB signaling pathway, as well as metastatic and angiogenic mediators. Anthos administered orally significantly decreased MDA-MB-231 orthoxenograft tumor volume and led to lower rates of lymph node and lung metastasis, compared to control. Treatment of PAC-resistant MDA-MB-231Tx cells with Anthos and PAC in combination lowered the IC50 of PAC by nearly 20-fold. The combination treatment also significantly (p < 0.01) decreased the tumor volume in MDA-MB-231Tx orthoxenografts, compared to control. In contrast, Anthos and PAC alone were ineffective against MDA-MB-231Tx tumors. Our approach of using Anthos to inhibit the growth and metastasis of breast cancers, as well as to chemosensitize PAC-resistant TNBC, provides a highly promising and effective strategy for the management of TNBC.

scholarly journals Highly Adaptable Triple-Negative Breast Cancer Cells as a Functional Model for Testing Anticancer Agents

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109487 ◽  
Author(s):  
Balraj Singh ◽  
Anna Shamsnia ◽  
Milan R. Raythatha ◽  
Ryan D. Milligan ◽  
Amanda M. Cady ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Functional Model

Improving the efficacy of chemotherapy drugs for the treatment of triple-negative breast cancers.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 107-107
Author(s):  
Behyar Zoghi ◽  
Peter Ravdin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
High Throughput ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Expression Profiles ◽  
Breast Cancers ◽  
Efficient Treatment ◽  
Chemotherapy Drugs

107 Background: Approximately 15-20% of all breast cancers account for triple-negative breast cancers that exhibit aggressive, distinct metastatic pattern and poor prognosis. More than 50% of patients with triple negative breast cancers develop chemoresistance and do not respond to chemotherapeutic drugs, leading to early relapse and shorter survival. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious cancer drugs. Methods: Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Results: Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Since miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that they represent more attractive targets than the single gene or gene product that is the target of conventional cancer treatments that are typically prone to drug resistance. Supporting this, we have recently demonstrated that miRNAs can be systemically delivered to treat breast cancer lung metastasis without any hepatotoxicity. In addition to being a potent therapeutic regimen, our preliminary analyses reveal that miRNAs can be bonafide early prognostic markers to monitor treatment response to specific drugs in triple-negative breast cancers. Conclusions: Taken together, these findings suggest that miRNA can serve as potent therapeutic adjuvants and although the data content of miRNA profiles is far less than that of gene expression profiles, by virtue of their ability to modulate entire spectrum of genes and pathways miRNAs have potential to be better classifiers for the prognosis and response to treatment of cancers. We believe that the identification of miRNAs that mediate chemoresistance could lead to more efficient treatment selection at the patient level and an improved response rates at the population level.

scholarly journals BSCI-15. Osteopontin plays a crucial role in invasiveness of triple negative breast cancer cells in the context of human microglia

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii4-iii4
Author(s):  
Kamil Wojnicki ◽  
Agata Kochalska ◽  
Katarzyna Poleszak ◽  
Adria-Jaume Roura ◽  
Ewa Matyja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Microglia

Abstract The triple-negative breast cancer (TNBC) is the most malignant among breast cancers and has the high risk of developing metastasis into the brain. Metastases of breast cancers are increasing and pose a clinical challenge as the current treatments are not effective due to the unique brain microenvironment for metastatic breast cancer cells. While the contribution of brain macrophages to the formation of the metastatic niche is established, factors responsible for the crosstalk between cells remain elusive. SPP1 encoding a secreted phosphoprotein 1 (ostepontin) is highly overexpressed in malignant breast cancers. We evaluated the role of SPP1 in invasion and metastasis of human breast cancer cells. We found the increased invasion of triple-negative MDA-MB-231 (MDA-231) cells in the presence of human microglial HMSV40 cells. Using Western blot analysis demonstrated the elevated levels of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) in MDA-231 cells in co-cultures. Moreover, blocking SPP1 and integrin interactions with the synthetic RGD peptide, efficiently diminished both basic and microglia-induced invasion of MDA-231. To assess the role of SPP1 in cell invasion, we established the MDA-231 cells with knocked-down SPP1 expression using shRNA (shSPP1). Interestingly, the shSPP1 cells were unresponsive towards HMSV40 microglia. We have previously found that an antibiotic minocycline reduces SPP1 expression in glioma cells. We performed cell toxicity studies on 4 breast cancer cell lines and various non-malignant cells. All tested malignant cancer cells were more sensitize to minocycline than non-cancerous cells and breast cancer cells derived from TNBC were the most susceptible. Altogether, we demonstrate that microglia support invasion of breast cancer cells via SPP1/osteopontin triggering the integrin signalling, and minocycline by downregulating SPP1 expression may reduce both basic and microglia-induced cancer invasion. Therefore, we purpose that minocycline could be a new therapeutics targeting metastatic brain cancers.

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