School Of Health Sciences
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Item Targeting Redox Homeostasis of Tumor Cells by Therapeutic Compounds in Cancer: An Indian Perspective(Springer Singapore, 2022-09-28T00:00:00) Vasudeva, Kanika; Chaturvedi, Pragya; Khan, Rahul; Sahu, Prachi; Munshi, AnjanaCancer is one of the significant causes of morbidity and mortality in the world. The role of oxidative stress in tumor progression and metastasis has been under focus since the last two decades, suggesting the importance of redox balance upon which cancer cells thrive to promote oncogenic phenotype. Therefore, it is highly warranted to develop therapies that can disrupt the fine-tuned intracellular reactive oxygen species (ROS) balance of tumor cells. Even though classical chemotherapy, radiotherapy, and many FDA-approved chemotherapeutic drugs modulate ROS levels, the associated side effects make it worthwhile to explore alternative options. Various compounds of natural origin have high efficacy and minimum side effects and pose a low risk of recurrence. This chapter has been compiled to give a thorough account of medicinal plants of Indian origin that have been implicated in ROS modulation and their potential applications in clinical settings. � Springer Nature Singapore Pte Ltd. 2022.Item Differential molecular mechanistic behavior of HDACs in cancer progression(Springer, 2022-08-16T00:00:00) Singh, Tashvinder; Kaur, Prabhsimran; Singh, Paramdeep; Singh, Sandeep; Munshi, AnjanaGenetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs� role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Design, Synthesis and Biological Evaluation of New 5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles as Topoisomerase Inhibitors(John Wiley and Sons Inc, 2021-07-09T00:00:00) Kaur, Manpreet; Mehta, Vikrant; Arora, Sahil; Munshi, Anjana; Singh, Sandeep; Kumar, Raj5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles are designed as topoisomerase (Topo) inhibitors, synthesised and assessed for their anticancer properties against breast (MDA-MB-231 and MCF7), lung (A549), and colorectal (HCT116) cancer cell lines. All the compounds induced significant cytotoxicity at low micromolar concentration. The compound 5e exerted potential anticancer effects on breast cancer cell lines at a low micromolar level (IC50<2 ?M), and showed negligible toxicity towards normal cells. Compound 5 e reduced reactive oxygen species (ROS) level in breast cancer cells, altered mitochondrial membrane potential and induced the cell cycle arrest at the G2/M phase. This was accompanied by downregulation of oncogenic p-Akt and upregulation of p-PTEN along with modulation of apoptotic markers suggesting multiple mechanisms to reduce cancer cell viability. Finally, the topoisomerase inhibition assay revealed the inhibitory activity of 5 e against Topo I and Topo II. � 2021 Wiley-VCH GmbH.