Botany - Research Publications

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INFLUENCE OF INSULIN AND METFORMIN ON PROSTATE CANCER
(Nova Science Publishers, 2017) Singh, Pushpendra; Bast, Felix; Kumar, Shashank; Saini, Khem Chand
Dietary habit and hormonal factor play a significant role in prostate cancer deregulation in addition to genetic and environmental factor. Nonandrogenic growth factor like insulin and insulin growth factor are influences the prostate cancer initiation and progression. Insulin and Insulin-like growth factor regulate various metabolic pathways, cell growth, cellular proliferation and apoptosis. Various epidemiological results point out that insulin not only increased the risk of cardiovascular, macrovascular, and microvascular complications but also at significantly increase the risk of various cancers. The use of metformin, the usually approved drug for type 2 diabetes, was continually linked with the decreased risk of the incidence of a variety of cancers. More than 60 clinical trials of metformin being tested as a treatment for various types of cancer, including breast, colon, prostate, endometrial, and pancreatic cancer. The ability of metformin to lower circulating insulin may be predominantly imperative for the treatment of cancers. Moreover, metformin inhibiting mammalian target of rapamycin promoted cell growth signaling. In this chapter, the confirmation behind a role for metformin in cancer therapy and its prospective molecular mechanisms of action are discussed.
Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; In silico and in vitro
(Springer New York LLC, 2015) Singh, Pushpendra; Bast, Felix
Myricetin is a naturally omnipresent benzo-?-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, owing to the evidences endorsed their over-expression on cancer cells. This study is a concerted effort to explore the potent and specific multi-targeted inhibitor against RTKs and AR\ER employing molecular docking approach. IR, IGF1R, EGFR, VEGFR1, VEGFR2, and AR\ER were chosen as a protein and natural compounds as a ligand. Molecular docking procedure followed by using Maestro 9.6 (Schr?dinger Inc). All natural compounds were docked with the X-ray crystal structures of selected proteins by employing grid-based ligand docking with energetics Maestro 9.6. IBS natural compounds docked with each selected protein molecules by using GLIDE high throughput virtual screening. On the basis of Gscore, we selected 20 compounds from IBS (50,000 compounds) along with 68 anticancer compounds from published literature for GLIDE extra precision molecular docking. Calculated docking free energy yielded the excellent dock score for the myricetin when docked with proteins EGFR, IR, and AR\ER. Protein-ligand interactions profile highlighted that the lipophilic, hydrogen bonding and ?-? stacking interactions play a central role in protein-ligand interactions at the active site. The results of MTT assay reveal that the myricetin inhibit the viability and proliferation of cancer cells in a dose-dependent manner. Treatment with the myricetin led to down-regulation of mRNA expression of EGFR, IR, mTOR, and Bcl-2. Although, further in vitro and in vivo experimental studies are required for the experimental validation of our findings. ? 2015 Springer Science+Business Media New York.
Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: Novel treatment strategies for cancer
(Humana Press Inc., 2014) Singh, Pushpendra; Alex, Jimi Marin; Bast, Felix
Insulin and insulin-like growth factor (IGF) signaling system, commonly known for fine-tuning numerous biological processes, has lately made its mark as a much sought-after therapeutic targets for diabetes and cancer. These receptors make an attractive anticancer target owing to their overexpression in variety of cancer especially in prostate and breast cancer. Inhibitors of IGF signaling were subjected to clinical cancer trials with the main objective to confirm the effectiveness of these receptors as a therapeutic target. However, the results that these trials produced proved to be disappointing as the role played by the cross talk between IGF and insulin receptor (IR) signaling pathways at the receptor level or at downstream signaling level became more lucid. Therapeutic strategy for IGF-1R and IR inhibition mainly encompasses three main approaches namely receptor blockade with monoclonal antibodies, tyrosine kinase inhibition (ATP antagonist and non-ATP antagonist), and ligand neutralization via monoclonal antibodies targeted to ligand or recombinant IGF-binding proteins. Other drug-discovery approaches are employed to target IGF-1R, and IR includes antisense oligonucleotides and recombinant IGF-binding proteins. However, therapies with monoclonal antibodies and tyrosine kinase inhibition targeting the IGF-1R are not evidenced to be satisfactory as expected. Factors that are duly held responsible for the unsuccessfulness of these therapies include (a) the existence of the IR isoform A overexpressed on a variety of cancers, enhancing the mitogenic signals to the nucleus leading to the endorsement of cell growth, (b) IGF-1R and IR that form hybrid receptors sensitive to the stimulation of all three IGF axis ligands, and (c) IGF-1R and IR that also have the potential to form hybrid receptors with other tyrosine kinase to potentiate the cellular transformation, tumorigenesis, and tumor vascularization. This mini review is a concerted effort to explore and fathom the well-recognized roles of the IRA signaling system in human cancer phenotype and the main strategies that have been so far evaluated to target the IR and IGF-1R. ? 2013 Springer Science+Business Media New York.

Botany - Research Publications

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