Deciphering the molecular mechanism underlying anticancer activity of coumestrol in triple-negative breast cancer cells

2018 ◽  
Vol 46 ◽  
pp. 19-28 ◽  
Author(s):  
Atif Zafar ◽  
Swarnendra Singh ◽  
Yatendra Kumar Satija ◽  
Daman Saluja ◽  
Imrana Naseem
Author(s):  
Sampath K. Banupriya ◽  
Krishnamoorthy Kavithaa ◽  
Arumugam Poornima ◽  
Sundaravadivelu Sumathi

Background: In the current era, development of molecular techniques involves nanotechniques and the synthesis of nanoparticles is considered as the preferred field in nanotechnology. Objective: The aim of the present work is to analyze the anticancer activity of the thymoquinone conjugated ZnO nanoparticles and to understand its mechanism of action in triple negative breast cancer cell line MDA-MB-231. Methods: Zinc Oxide (ZnO) nanoparticles have extensive applications and it was synthesized using a chemical precipitation method. Thymoquinone (TQ) is the major bioactive component of the seeds of Nigella sativa. Synthesized nanoparticles were characterized using various spectroscopic techniques. Thymoquinone coated nanoparticles were checked for its efficiency. The cytotoxicity of ZnO, TQ and TQ conjugated ZnO nanoparticles against MDA-MB-231. Colony forming and cell migration assay were performed to measure the proliferative competence of the breast cancer cells on exposure to nanoparticles. The mechanism of apoptosis was probed by assessing MMP, interplay between ER stress and ROS. Results: The results of the characterization techniques confirmed the particles synthesized were ZnO and TQ-ZnO nanoparticles. pH dependent release of the compound was observed. Anti-proliferative effect that impairs the formation of colony was found to be enhanced in cells exposed to combined treatment with the nanoconjugate. Conclusion: Hence, the TQ conjugated ZnO nanoparticles can act as an efficient carrier for drug delivery at the target site in TNBC cells.


BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Mathangi Ravi ◽  
Shilpa Tentu ◽  
Ganga Baskar ◽  
Surabhi Rohan Prasad ◽  
Swetha Raghavan ◽  
...  

2020 ◽  
Vol 22 (2) ◽  
pp. 1213-1226
Author(s):  
Samia Messeha ◽  
Najla Zarmouh ◽  
Patricia Mendonca ◽  
Carolyn Cotton ◽  
Karam Soliman

2019 ◽  
Vol 43 (29) ◽  
pp. 11784-11794 ◽  
Author(s):  
María R. Rodríguez ◽  
Lucía M. Balsa ◽  
Julián Del Plá ◽  
Javier García-Tojal ◽  
Reinaldo Pis-Diez ◽  
...  

New vanadium complex was synthesized and fully characterized showing promising anticancer activity on triple negative breast cancer cells.


2020 ◽  
Author(s):  
Gemma Serra-Bardenys ◽  
Tian Tian ◽  
Enrique Blanco ◽  
Jessica Querol ◽  
Laura Pascual-Reguant ◽  
...  

SUMMARYThe histone modification of H3 oxidized at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase–like 2 (LOXL2) and is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells. Although H3K4ox has been linked to the maintenance of compacted chromatin, the molecular mechanism underlying this maintenance is unknown. Here we show that H3K4ox is read by the CRL4B complex, leading to the ubiquitination of histone H2A through the E3 ligase RBX1. Finally, interactions between RUVBL1/2 and LOXL2 are involved in the incorporation of the histone variant H2A.Z, which plays an essential role in the mechanism controlling the dynamics of oxidized H3. Maintenance of H3K4ox in chromatin is essential for heterochromatin properties, and disruption of any of the members involved in this pathway blocks the oncogenic properties of TNBC cells.


2020 ◽  
Author(s):  
LIU LIU ◽  
Qiufeng Lao ◽  
Shengle Li ◽  
Weiyi Pang

Abstract BackgroundDioscorea bulbifera L. is mainly used for antitumor therapy in clinical practice. Studies have shown that the drug-containing serum obtained from Dioscorea bulbifera L. induces the apoptosis and inhibits the proliferation of rat breast cancer cells. However, the main active compounds and the molecular mechanism in triple-negative breast cancer are still unclear.MethodsThe TCMSP, GeneCards, GEO and TCGA databases were used to identify genes that intersect the target genes of Dioscorea bulbifera L., active Dioscorea bulbifera L. components and triple-negative breast cancer targets, and Kaplan-Meier and GSEA methods were used to analyze the survival and pathway enrichment of the intersecting genes, respectively. Subsequently, in vitro experiments were performed for verification.ResultsA total of 14 active components were screened, and the targets of the active components were combined with triple-negative breast cancer-related targets and differentially expressed genes obtained from the GeneCards database. Three genes (CCNB1, PGR and TP63) are related to the anti-breast cancer effects of Dioscorea bulbifera L., and TP63 (P<0.05) is related to breast cancer survival. The GSEA showed that the TP63 gene is related to the apoptosis pathway, and TP63 gene analysis in the TCGA clinical database showed the greatest expression difference in triple-negative breast cancer. The in vitro experiments showed that diosbulbin B, the main antitumor compound in Dioscorea bulbifera L., may inhibit the proliferation and migration of MDA-MB-231 breast cancer cells and induce their apoptosis by promoting the expression of the TP63 gene.ConclusionThe present study fully elucidated the active components, potential targets and molecular mechanisms of Dioscorea bulbifera L. against triple-negative breast cancer and provided a new method for revealing the scientific basis and therapeutic mechanism of Chinese medicine in treating diseases.


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