Emerging perspectives: unraveling the anticancer potential of vitamin D3.

Vitamin D3, a fat-soluble vitamin known for its critical function in calcium homeostasis and bone health, is gaining interest for its anticancer properties. Observational studies have suggested a negative relationship between vitamin D levels and the incidence of some malignancies throughout the years, prompting substantial investigation to find its anticancer effects. The purpose of this comprehensive review is to investigate the diverse function of vitamin D3 in cancer prevention and therapy. We explored the molecular mechanism underlying its effects on cancer cells, which range from cell cycle control and death to angiogenesis and immune response modulation. Insights from in vitro and in vivo studies provide valuable evidence supporting its anticancer potential. Furthermore, we look at epidemiological and clinical studies that investigate the relationship between vitamin D3 levels and cancer risk or treatment results. Vitamin D3 supplementation's safety profile and cost-effectiveness increase its attractiveness as an adjuvant therapy in conjunction with traditional treatment regimens. Our critical review of the current literature provides an in-depth understanding of vitamin D3's anticancer effect, covering the obstacles and possibilities in realizing its promise for cancer prevention and therapy. The findings of this study might pave the way for the development of innovative treatment techniques that take use of the advantages of vitamin D3 to fight cancer and improve patient care. As research progresses, a better understanding of vitamin D3's anticancer processes will surely simplify its incorporation into personalized cancer care techniques, hence enhancing patient outcomes in the battle against cancer.

Alysicarpus vaginalis Bio-Actives as ESR Signaling Pathway Inhibitor for Breast Cancer Treatment: A Network Pharmacology Approach.

In our previous study Alysicarpus vaginalis (AV) has appeared as a promising target for breast cancer hence we have screened potential targets by in silico, In Vitro and In Vivo methods. A network pharmacology (NP) approach involves prediction and validating of targets via molecular modeling, western blotting and In Vivo MNU-induced mammary cancer. The PPI network showed the 573 edges between 214 nodes (targets) that are involved in breast cancer and important one are ESR-1, ESR-2, AR, EGFR, NOS3, MAPK, KDR, SRC and MET. Compound-target-pathway network involves 04 compounds and 221 interactive protein targets associated with breast cancer. GO and KEGG enrichment analysis predicted the ERR, c-MET, PDGFR-α/ß, EGFR, and VEGF as a key targets in the breast cancer treatment which are validated via molecular modeling. Expression of ER-α, AR and EGFR were significantly down regulated by AV in MCF-7 cell line. In addition, the immunoreactivity of ER-α was reduced significantly in MNU-induced mammary carcinoma, which is a key target in ER + breast cancer. Overall, this study scientifically light ups the pharmacological mechanism of AV in the treatment of breast cancer, strongly associated with the regulation of ESR signaling pathway.

Network analysis and molecular mapping for SARS-CoV-2 to reveal drug targets and repurposing of clinically developed drugs.

Novel coronavirus (SARS-CoV-2), turned out to be a global pandemic with unstoppable morbidity and mortality rate. However, till date there is no effective treatment found against SARS-CoV-2. We report on the major in-depth molecular and docking analysis by using antiretroviral (Lopinavir and ritonavir), antimalarial (Hydroxychloroquine), antibiotics (Azithromycin), and dietary supplements (Vitamin C and E) to provide new insight into drug repurposing molecular events involved in SARS-CoV-2. We constructed three drug-target-pathways-disease networks to predict the targets and drugs interactions as well as important pathways involved in SARS-CoV-2. The results suggested that by using the combination of Lopinavir, Ritonavir along with Hydroxychloroquine and Vitamin C may turned out to be the effective line of treatment for SARS-CoV-2 as it shows the involvement of PARP-1, MAPK-8, EGFR, PRKCB, PTGS-2, and BCL-2. Gene ontology biological process analysis further confirmed multiple viral infection-related processes (P < 0.001), including viral life cycle, modulation by virus, C-C chemokine receptor activity, and platelet activation. KEGG pathway analysis involves multiple pathways (P < 0.05), including FoxO, GnRH, ErbB, Neurotrophin, Toll-like receptor, IL-17, TNF, Insulin, HIF-1, JAK-STAT, Estrogen, NF-kappa, Chemokine, VEGF, and Thyroid hormone signaling pathway in SARS-CoV-2. Docking study was carried out to predict the molecular mechanism Thus, the potential drug combinations could reduce viral infectivity, viral replication, and abnormal host inflammatory responses and may be useful for multi-target drugs against SARS-CoV-2.

A network pharmacology-based approach to explore potential targets of Caesalpinia pulcherima: an updated prototype in drug discovery.

Caesalpinia pulcherima (CP) is a traditional herb used for the treatment of asthma, bronchitis, cancer, anti-bacterial, anti-fungal and as abortifacient. In the present study, bioactive components and potential targets in the treatment of breast cancer validated through in silico, in vitro and in vivo approach. The results for the analysis were as among 29 components, only four components were found active for further study which proved the use of CP as a multi-target herb for betterment of clinical uses. The results found by PPI states that our network has significant interactions which include the ESR-1, ESR-2, ESRRA, MET, VEGF, FGF, PI3K, PDK-1, MAPK, PLK-1, NEK-2, and GRK. Compound-target network involves 4 active compound and 150 target genes which elucidate the mechanisms of drug action in breast cancer treatment. Furthermore, on the basis of the above results the important proteins were fetched for the docking study which helps in predicting the possible interaction between components and targets. The results of the western blotting showed that CP regulates ER and EGFR expression in MCF-7 cell. In addition to this animal experimentation showed that CP significantly improved immunohistological status in MNU induced carcinoma rats. Network pharmacology approach not only helps us to confirm the study of the chosen target but also gave an idea of compound-target network as well as pathways associated to the CP for treating the complex metabolic condition as breast cancer and they importance for experimental verification.

Chemomodulatory effects of Alysicarpus vaginalis extract via mitochondria-dependent apoptosis and necroptosis in breast cancer.

The present study intended to assess the anticancer potential of Alysicarpus vaginalis ethyl acetate fraction (AVEAF) in breast cancer cell lines (MCF-7 and MDA-MB-453) and against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in Sprague-Dawley rats which resemble the human estrogen dependent breast cancer. The SRB assay showed that the maximum growth inhibition rate of AVEAF on MCF-7 cell was 27.12 at 100 µg/ml. Flow cytometry analysis observed that AVEAF induced the cell cycle arrest at the S phases and decreased in mitochondrial membrane potential on the MCF-7 cells. AVEAF elevated intracellular ROS level in the MCF-7 cells which were reversed with N-acetycysteine (2 mM) pretreatment indicating that AVEAF induced mitochondrial-mediated apoptosis via augmentation of intracellular ROS. Western blotting exhibited that AVEAF increased the expression of pro-apoptotic protein Bax while decreasing anti-apoptotic proteins Bcl-2 and Bcl-xL expression which promoted the cleavage of caspase-9, PARP1, RIPK 1, and RIPK 3. Additionally, AVEAF exerted anticancer effect on tumor-bearing rats and the tumor inhibition rate is 50%. Data of the study indicate that AVEAF exhibits In Vitro and In Vivo anticancer activities that associate with its ROS-mediated mitochondrial-mediated intrinsic pathway of apoptosis and necroptosis in MCF-7 cells and may serve as a potential against breast cancer.

Design, synthesis and anticancer screening of 3-(3-(substituted phenyl) acryloyl)-2H-chromen-2ones as selective anti-breast cancer agent.

By utilizing concept of molecular hybridization, involving combination of various Pharmacophore, novel substituted coumarin-chalcone hybrids was synthesized and evaluated for anti-proliferative activity against estrogen receptor-positive MCF-7 and negative MDA-MB-435 breast cancer cell lines. In-vivo study was carried out by N-methyl nitrosourea (MNU) induced mammary carcinoma in virgin female Spraque Dawly (SD) rats. The compound 5b has highest potential than standard drug Adriamycin, comparable against Tamoxifen against ER-positive MCF-7 breast cancer cell lines. Docking study was performed to study the binding orientation and affinity of synthesized compounds on the ER-α enzyme.