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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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Related Experiment Video

Updated: May 31, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

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Ezetimibe Anticancer Activity via the p53/Mdm2 Pathway.

Charmy Twala1, Sibusiso Malindisa1, Chamone Munnik1

  • 1Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Cnr. Pioneer and Christiaan de Wet Roads, B2-010 Calabash Building, Florida, Johannesburg 1710, South Africa.

Biomedicines
|January 25, 2025
PubMed
Summary
This summary is machine-generated.

Ezetimibe, a cardiovascular drug, shows potential anticancer activity by inhibiting Mdm2 and cancer cell growth. Further research may combine it with RBBP6 inhibitors for enhanced efficacy.

Keywords:
EzetimibeMdm2cancerdrug designdrug developmentdrug repurposingp53

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Ezetimibe is a cardiovascular drug that inhibits the Niemann-Pick C1-Like 1 (NPC1CL1) protein.
  • Emerging evidence suggests Ezetimibe may possess anticancer properties through cholesterol reduction or specific signaling pathways.

Purpose of the Study:

  • To investigate the potential anticancer mechanisms of Ezetimibe.
  • To evaluate Ezetimibe's binding affinity to Mdm2 and its effect on cancer cell lines.

Main Methods:

  • In silico studies including molecular docking were performed to assess Ezetimibe's binding to the Mdm2 protein.
  • The binding energies of Ezetimibe and other inhibitors (RG7388, RG7112) were compared.
  • The effect of Ezetimibe on cancer cell line growth was assessed at various concentrations.

Main Results:

  • Ezetimibe demonstrated strong binding to the Mdm2 protein's p53 binding domain, forming a stable complex.
  • Ezetimibe exhibited lower binding energies compared to RG7388 and RG7112.
  • Ezetimibe inhibited the growth of multiple cancer cell lines at non-toxic concentrations for normal cells.

Conclusions:

  • Ezetimibe shows potential efficacy against cancers overexpressing Mdm2.
  • Combination therapy with RBBP6 inhibitors could enhance Ezetimibe's anticancer activity.
  • Parenteral administration of Ezetimibe is recommended for cancer treatment due to poor oral bioavailability.