Department of Biological Sciences

Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1922

Browse

Author: search.filters.author.Mukherjee, SudeshnaSubject: search.filters.subject.Cancer

Search Results

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    Metal-free, visible-light-mediated synthesis of tetracyclic benzimidazole: regioselective c–h functionalization with in vitro and computational study of anti-breast cancer compounds
    (ACS, 2025-02) Murugesan, Sankaranarayanan; Mukherjee, Sudeshna
    Globally, breast cancer is the leading cause of mortality. Within the field of antibreast cancer drug design by several compound docking studies, eight new N-containing nonsteroid tetracyclic derivatives have been synthesized via regioselective intramolecular C–H functionalization by visible light. The adopted methodology is highly efficient, green, and sustainable to unload a new pathway with excellent yield. It offers a rapid, low-cost, catalyst-free method for creating physiologically active molecules from easily accessible substrates. The synthesized substances were described using spectroscopic methods like HRMS, 1HNMR, 13CNMR, and XRD analysis. This study explores the cytotoxic potential of novel compounds against human MCF-7 breast cancer cells. This study includes in vitro experiments to assess the effect of our compounds on cells. These experiments include cytotoxicity assessment by cell cycle, apoptosis, MTT test analysis by flow cytometry, reactive oxygen species (ROS) production assessment, etc. Among the novel compounds, compound 2e exhibited the most potent cytotoxic activity, with an inhibitory concentration (IC50) of 40 nM, surpassing the efficacy of established drugs such as exemestane (IC50 24.97 micromolar) and tamoxifen (IC50 5.45 μM). Compound 2e also significantly induced apoptosis and cell cycle arrest in the G1 phase, increasing the apoptotic cell population to 65.97%. Additionally, the compound led to a marked rise in the level of ROS generation, implicating oxidative stress in its mechanism of action. Molecular docking and dynamic simulation further supported the vigorous anticancer activity of compound 2e, demonstrating its promise as an effective breast cancer treatment.
  • No Thumbnail Available
    Item
    Epigenetic adaptations in drug-tolerant tumor cells
    (Elsevier, 2023) Chowdhury, Rajdeep; Chowdhury, Shibasish; Mukherjee, Sudeshna
    Traditional chemotherapy against cancer is often severely hampered by acquired resistance to the drug. Epigenetic alterations and other mechanisms like drug efflux, drug metabolism, and engagement of survival pathways are crucial in evading drug pressure. Herein, growing evidence suggests that a subpopulation of tumor cells can often tolerate drug onslaught by entering a “persister” state with minimal proliferation. The molecular features of these persister cells are gradually unraveling. Notably, the “persisters” act as a cache of cells that can eventually re-populate the tumor post-withdrawal drug pressure and contribute to acquiring stable drug-resistant features. This underlines the clinical significance of the tolerant cells. Accumulating evidence highlights the importance of modulation of the epigenome as a critical adaptive strategy for evading drug pressure. Chromatin remodeling, altered DNA methylation, and de-regulation of non-coding RNA expression and function contribute significantly to this persister state. No wonder targeting adaptive epigenetic modifications is increasingly recognized as an appropriate therapeutic strategy to sensitize them and restore drug sensitivity. Furthermore, manipulating the tumor microenvironment and “drug holiday” is also explored to maneuver the epigenome. However, heterogeneity in adaptive strategies and lack of targeted therapies have significantly hindered the translation of epigenetic therapy to the clinics. In this review, we comprehensively analyze the epigenetic alterations adapted by the drug-tolerant cells, the therapeutic strategies employed to date, and their limitations and future prospects.
  • No Thumbnail Available
    Item
    Cytoplasmic Signaling Circuitry: An Important Trait of Cancer
    (Taylor & Francis, 2018) Mukherjee, Sudeshna
  • No Thumbnail Available
    Item
    Cancer: an evolutionary perspective
    (Sci Medical, 2015) Chowdhury, Rajdeep; Mukherjee, Sudeshna
    Cancer is intricately linked to our evolutionary history. The origin and progression of cancer can hence be better understood when viewed from an evolutionary perspective. In this review, we portray the fundamental fact that within the complex ecosystem of the human body, the cancerous cells also evolve. Just like any organism, they face diverse selective pressure to adapt to the tumor environment. There exists a competitive struggle that eliminates the unfit, leaving the well-adapted to thrive. Sequential acquisition of “driver mutations”, chromosomal instability triggering macromutations and punctuated bursts of genetic changes can all hypothetically contribute to the origin and evolution of cancer. We further describe that like in any ecosystem, cancer evolution involves not just the cancerous cells but also its interaction with the environment. However, as cancer evolves, individual cells behave more like a unicellular organism focused on its own survival. We also discuss evidences where cancer has evolved through transmission between individuals. An evolutionary analogy can open up new vistas in the treatment of this dreadful disease