Establishment of a bioluminescent MDA-MB-231 cell line for human triple-negative breast cancer research

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.

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Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis

Cancers ◽

10.3390/cancers13153871 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3871

Author(s):

Emma Rodriguez ◽

Guangsheng Pei ◽

Sang T. Kim ◽

Alexis German ◽

Prema Robinson

Keyword(s):

Breast Cancer ◽

Flow Cytometry ◽

Cell Line ◽

Pc12 Cells ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Therapeutic Option ◽

Neuronal Cell ◽

Receptor Antagonism ◽

Tnbc Cell

Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. There is critically important to find new, effective and safe therapeutics for TNBC. We determined if SP-receptor antagonism in combination with cisplatin may serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. We used a neuronal cell line (PC12) and two TNBC cell lines (Sum 185 and Sum 159) for these studies. We determined that the levels of cells expressing the high-affinity SP-receptor (neurokinin 1 receptor (NK1R)), as determined by flow-cytometry was significantly elevated in response to cisplatin in all three cells. We determined that treatment with aprepitant, an SP-receptor antagonist decreased cisplatin-induced, loss of viability (studied by MTT assay), production of reactive oxygen species (by DCFDA assay) and apoptosis (by flow-cytometry) in PC12 cells while it was increased in the two TNBC cells. Furthermore, we demonstrated that important genes associated with metastases, inflammation, chemoresistance and cell cycle progression are attenuated by SP-receptor antagonism in the TNBC cell line, Sum 185. These studies implicate that SP-receptor antagonism in combination with cisplatin may possibly serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC.

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Growth Promotion and Increased ATP-Binding Cassette Transporters Expression by Liraglutide in Triple Negative Breast Cancer Cell Line MDA-MB-231

Drug Research ◽

10.1055/a-1345-7890 ◽

2021 ◽

Author(s):

Amir Shadboorestan ◽

Parastoo Tarighi ◽

Mahsa Koosha ◽

Homa Faghihi ◽

Mohammad Hossein Ghahremani ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Triple Negative Breast Cancer ◽

Abc Transporters ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Growth Promotion ◽

Atp Binding ◽

Mesenchymal Transition ◽

Atp Binding Cassette

Background Glucagon-like petide-1 (GLP-1) agonists such as liraglutide are widely employed in type 2 diabetes due to their glucose reducing properties and small risk of hypoglycemia. Recently, it has been shown that GLP-1agonists can inhibit breast cancer cells growth. Nonetheless, concerns are remained about liraglutide tumor promoting effects as stated by population studies. Material and Methods We evaluated the effects liraglutide on proliferation of MDA-MB-231 cells by MTT assay and then ATP-binding cassette (ABC) transporters expressions assessed by Real time PCR. Statistical comparisons were made using one-way analysis of variance followed by a post hoc Dunnett test. Results Here, we report that liraglutide can stimulate the growth of highly invasive triple negative cell line MDA-MB-231; which can be attributed to AMPK-dependent epithelial-mesenchymal transition (EMT) happening in MDA-MB-231 context. Toxicity effects were only observed with concentrations far above the serum liraglutide concentration. ATP-binding cassette (ABC) transporters expressions were upregulated, indicating the possible drug resistance and increased EMT. Conclusion In conclusion, these results suggest that liraglutide should be used with caution in patients who are suffering or have the personal history of triple negative breast cancer. However, more detailed studies are required to deepen understanding of liraglutide consequences in triple negative breast cancer. ▶Graphical Abstract.

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Discovery and SAR studies of novel 2-anilinopyrimidine-based selective inhibitors against triple-negative breast cancer cell line MDA-MB-468

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2018.11.010 ◽

2019 ◽

Vol 29 (1) ◽

pp. 62-65 ◽

Cited By ~ 5

Author(s):

Jeyun Jo ◽

Sou Hyun Kim ◽

Heegyu Kim ◽

Myeonggyo Jeong ◽

Jae-Hwan Kwak ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cell Line ◽

Triple Negative ◽

Cancer Cell Line ◽

Selective Inhibitors ◽

Sar Studies

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Inhibition of PI3K/Akt/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38

BMC Cancer ◽

10.1186/s12885-017-3695-5 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 20

Author(s):

Katharina Gohr ◽

Alexandra Hamacher ◽

Laura H. Engelke ◽

Matthias U. Kassack

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cell Line ◽

Triple Negative ◽

Cisplatin Resistance ◽

Cancer Cell Line

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Meroterpenoids From Ganoderma lucidum Mushrooms and Their Biological Roles in Insulin Resistance and Triple-Negative Breast Cancer

Frontiers in Chemistry ◽

10.3389/fchem.2021.772740 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jiao-Jiao Zhang ◽

Dai-Wei Wang ◽

Dan Cai ◽

Qing Lu ◽

Yong-Xian Cheng

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Cell Line ◽

Triple Negative Breast Cancer ◽

Ganoderma Lucidum ◽

Triple Negative ◽

Raw Materials ◽

Biological Evaluation ◽

C2c12 Cells ◽

Dependent Manner

Ganoderma fungi as popular raw materials of numerous functional foods have been extensively investigated. In this study, five pairs of meroterpenoid enantiomers beyond well-known triterpenoids and polysaccharides, dayaolingzhiols I−M (1–5), were characterized from Ganoderma lucidum. Their structures were identified using spectroscopic and computational methods. Structurally, compound 1 features a novel dioxabicyclo[2.2.2]octan-3-one motif in the side chain. Ethnoknowledge-derived biological evaluation found that (+)-5 could activate Akt and AMPK phosphorylation in insulin-stimulated C2C12 cells, and (+)-5 could activate glucose uptake dose dependently in C2C12 cells. Furthermore, we found that (+)-1 (+)-4, and (–)-4 could significantly inhibit cell migration of the MDA-MB-231 cell line, of which (+)-4 showed significant inhibitory effects against cell migration of the MDA-MB-231 cell line in a dose-dependent manner. These findings revealed the meroterpenoidal composition of G. lucidum and its roles in the prevention of chronic diseases such as diabetes mellitus and triple-negative breast cancer.

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