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Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Published on: June 26, 2018
Recent Perspectives on Anticancer Potential of Coumarin Against Different Human Malignancies: An Updated Review
Muhammad Shahbaz1, Asfa Perween2, Ushna Momal1
1Department of Food Science and Technology Muhammad Nawaz Shareef University of Agriculture Multan Multan Pakistan.
Abstract:
Coumarins, a group of naturally occurring compounds, have been reported to demonstrate anticancer potential. These substances, distinguished by their combined benzene and α-pyrone rings, have been demonstrated to impact multiple cellular mechanisms essential for the initiation and advancement of cancer. These agents work in different ways that prevent different tumor cells from growing, spreading, and increasing. One of the main anticancer mechanisms of coumarin act is killing cancer cells through apoptosis. This includes changes to pro- and anti-apoptotic proteins like Bcl-2 and Bax, the release of cytochrome c from mitochondria, and the activation of caspases. The tumor suppressor protein p53's expression has been discovered to be upregulated by coumarins such as esculetin and imperatorin, which encourage interrupted cell cycle and death. Additionally, coumarin has anti-angiogenic qualities, which are critical for the development and spread of tumors. It can slow the development of new blood vessels that feed tumors by inhibiting the "vascular endothelial growth factor (VEGF)" route of signaling. Coumarins inhibit the number of signaling pathways that are vital for cell division. For example, they can suppress the "PI3K/mTOR" pathway, which usually impairs the cancer cells and results in decreased cell viability and growth. Finally, coumarins could modulate the response of the immune system to cancerous cells. They have the ability to boost the activity of natural killer cells and cytotoxic T lymphocytes, which aid the immune system in identifying and eliminating cancer cells. Through a variety of mechanisms, such as immune response regulation, angiogenesis reduction, cell growth inhibition, and apoptosis activation, coumarins exhibit their anticancer effects. These molecular pathways demonstrate coumarins' potential as an interesting option for the development of novel anticancer treatments. More studies are needed to completely understand their modes of action and maximize their therapeutic efficacy.
Insights
Coumarins, natural compounds, show anticancer promise by inducing cancer cell death, inhibiting tumor growth, and boosting immune response. Further research is needed to fully utilize their therapeutic potential.
Area of Science:
- Natural Products Chemistry
- Pharmacology
- Oncology
Background:
- Coumarins are naturally occurring compounds with a distinct benzene and α-pyrone ring structure.
- These compounds have demonstrated significant potential in combating cancer through various cellular mechanisms.
Purpose of the Study:
- To explore the multifaceted anticancer mechanisms of coumarins.
- To elucidate how coumarins impact key cellular pathways involved in cancer initiation and progression.
Main Methods:
- Review of existing literature on coumarin's anticancer properties.
- Analysis of coumarin's effects on apoptosis, cell cycle regulation, angiogenesis, and immune response.
Main Results:
- Coumarins induce apoptosis by altering Bcl-2/Bax proteins, releasing cytochrome c, and activating caspases.
- They upregulate tumor suppressor p53, inhibit angiogenesis via VEGF signaling, and suppress PI3K/mTOR pathways.
- Coumarins modulate immune response by enhancing natural killer and cytotoxic T lymphocyte activity.
Conclusions:
- Coumarins exhibit anticancer effects through apoptosis induction, angiogenesis inhibition, cell growth suppression, and immune modulation.
- These diverse molecular actions highlight coumarins as promising candidates for novel anticancer drug development.
- Further investigation is crucial to fully understand their mechanisms and optimize therapeutic efficacy.
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