Chittaranjan National Cancer Institute

Bone marrow mesenchymal stem cells, also known as BMSCs, have been demonstrated to promote epithelial-to-mesenchymal transition (EMT) in triple-negative breast cancer (TNBC) cells, which contributes to the invasive and metastatic features of these cells. To be more specific, exosomes generated from bone marrow-derived mesenchymal stem cells (BMSC) that include microRNAs like miR-210-3p have the ability to activate the Wnt/β-catenin pathway, which further promotes the advancement of TNBC. Factors like as TGF-β and HGF are included in the BMSC secretome, which is a collection of chemicals that are released. These factors have the potential to contribute to extracellular matrix (ECM) and other aggressive behaviours like TNBC. Variable 2D and 3D models have been explored over the years to generate stable phenotyping characteristics of EMT in triple-negative breast cancer. Within the scope of this review, we have provided an in-depth analysis of the pathophysiology of EMT in breast cancer, as well as the varied crosstalk that occurs between distinct signalling pathways. A variety of in vivo and patient-derived xenograft models have been reviewed, along with their respective applications and possible limitations. This article provides a comprehensive discussion on the several cutting-edge 3D microphysiological disease models (Organoid, Spheroid, and Organ-on-Chip) that facilitate the replication of the pathophysiology of EMT in breast cancer. We have critically discussed our experimental observation on BMSC mediated co-conditioning and parallel cell homing with MDA-MB-231 to induce stable EMT. It will act as a marker pathway for medication targeting, treatments, and emphasis on drug resistance as a 3D in vitro microphysiological disease model.

Objective: To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus (Pers.) Morgan (A. hygrometricus) on human acute lymphoblastic leukemia cells. Methods: Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms, A. hygrometricus, Phallus sp., Lentinus sp., Tricholoma sp., and Serpula sp. was performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis determination, cell cycle profiling, intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and mitochondrial membrane potential were analyzed by flow cytometry. The activity of caspases was measured colorimetrically, and the expression pattern of mitochondrial proteins was analyzed. Results: The methanol extract of A. hygrometricus and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line, respectively. The mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 stage. The extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 cells. The methanol extract induced apoptosis by downregulating the expression of Bcl-2, increasing the expression of Bax, and activating the caspase cascade. Conclusion: The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.

In this study, we aimed to understand the interplay of the epigenetic modifier genes DNMT1 and TET1 along with HPV infection in the cervical epithelium and how it changes during tumorigenesis. For this purpose, initially the bioinformatical analysis (methylation and expression profile) of DNMT1 and TET1 was analyzed in the TCGA dataset. Next genetic (deletion) and epigenetic profiling (promoter methylation) of DNMT1 and TET1 were done in our sample pool and also validated in CACX cell lines as well. The results were further correlated with different clinicopathological parameters. Our data revealed that HPV infection in basal/parabasal layers of cervical epithelium actually disrupts the epigenetic homeostasis of DNMT1 and TET1 proteins which ultimately leads to the high expression of DNMT1 along with further reduction in TET1 protein during the development of carcinoma. Further, in-depth look into the results revealed that comparatively low methylation frequency of DNMT1 coupled with high promoter methylation and deletion frequency [22-46%] of TET1 were the plausible reasons of their antagonistic expression profile during the progression of the disease. Interestingly, the prevalence of DNMT1 [9.1%] and TET1 promoter methylation [22.7%] found in both the plasma DNA of the respective CACX patients implicated its diagnostic importance in this study. Lastly, molecular alteration of TET1 alone or in combination with DNMT1 showed the worst overall survival among the patients. Hence, it may be concluded that an inverse molecular profile of DNMT1 and TET1 genes seen in the proliferative basal-parabasal layers of the cervical epithelium was aggravated during the development of CACX along with genetic and epigenetic changes due to HPV infection.

Accurate and selective recognition of ions and molecules is crucial in medical and diagnostic research. Cu(II)- and Zn(II)-based coordination polymers (CPs) have been designed in this work to detect trace levels of melatonin and tryptophan and evaluate their anticancer activity. The [Cu2(4-bph)2(adc)4]n (CP1) (4-bph = (1E,2E)-1,2-bis(pyridin-4-ylmethylene) hydrazine; Hadc = 1-adamantanecarboxylic acid) structure shows that 4-bph serves as a bridging pyridyl-N ligand and adc- is a chelating and binuclear bridging ligand, forming an eight-membered Cu(μ-COO)2Cu motif. In Zn(II)-CP, 4-bph is a bridging ligand, while adc- is monodentate, yielding [Zn(4-bph)(adc)2]n (CP2). In CP1, π-π stacking (∼3.875 Å) and hydrogen bonding generate a 3D supramolecular network while CP2 forms pyridyl-N bridging zigzag 1D CP. The BET analysis measures higher pore volume of CP1 (0.06 cm3 g-1) than CP2 (0.018 cm3 g-1). The CP1 is weakly emissive, and upon irradiation at 312 nm, it emits at 392 nm which has been enhanced by the addition of tryptophan (Trp) (LOD, 44.65 nM), in the presence of 19 other amino acids. The CP1 senses melatonin (MEL) (LOD, 38 nM) also in the presence of various proteins, enzymes, and neuroactive metal ions. Blood serum is used for the measurement of melatonin in blood serum (pH 7.4) and also tryptophan measurement in milk. The CP2 is inactive toward sensing performance. DFT computation using crystallographic parameters reveals a stronger binding of CP1 with Trp (-221 kcal mol-1) than that of CP2 (-38.22 kcal mol-1). Anticancer assays show that CP1 is more potent than CP2 against MCF-7 breast cancer cells, IC50 values are 196.8 ± 2.31 nM (CP1) and 258.2 ± 2.08 nM (CP2). Both CPs exhibit minimal toxicity toward normal PBMCs at these doses. Theoretical evaluation has also been used to explain the luminescence and selective sensing behavior to Trp and MEL.