Curcumin arrests G-quadruplex in the nuclear hyper-sensitive III element of oncogene leading to apoptosis in metastatic breast cancer cells.

is deregulated in triple negative breast cancer (TNBC) pointing to be a promising biomarker for breast cancer treatment. Precise level of expression is important in the control of cellular growth and proliferation. Designing of -targeted antidotes to restore its basal level of cellular expression holds an optimistic approach towards anti-cancer treatment. transcription is dominantly controlled by Nuclear Hypersensitive Element III-1 (NHE) upstream of the promoter region possessing G-Quadruplex silencer element (). We have investigated the selective binding-interaction profile of a natural phytophenolic compound Curcumin with native G-quadruplex by conducting an array of biophysical experiments and based Molecular Docking and Molecular Dynamic (MDs) simulation studies. Curcumin possesses immense anti-cancerous properties. We have observed significantly increased stability of -G Quadruplex and thermodynamic spontaneity of Curcumin- GQ binding with negative ΔG value. Transcription of is tightly regulated by a complex mechanism involving promoters, enhancers and multiple transcription factors. We have used Curcumin as a model drug to understand the innate mechanism of controlling deregulated back to its basal expression level. We have checked -expression at transcriptional and translational level and proceeded for Chromatin Immuno-Precipitation assay (ChIP) to study the occupancy level of SP1, Heterogeneous nuclear ribonucleoprotein K (hnRNPK), Nucleoside Diphosphate Kinase 2 (NM23-H2) and Nucleolin at NHE upon Curcumin treatment of MDA-MB-231 cells. We have concluded that Curcumin binding tends to drive the equilibrium towards stable G-quadruplex formation repressing back to its threshold-level. On retrospection of the synergistic effect of upregulated and in cancer, we have also reported a new pathway [axis] through which Curcumin trigger apoptosis in cancer cells.Communicated by Ramaswamy H. Sarma.