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The Intrinsic Apoptotic Pathway01:31

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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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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
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Doramectin Induces Apoptosis in B16 Melanoma Cells.

Megan S Crotts1,2, Jena C Jacobs1,2, Robert W Baer1,2

  • 1Department of Biochemistry, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, Missouri, USA.

Anti-Cancer Agents in Medicinal Chemistry
|October 16, 2024
PubMed
Summary

Doramectin treatment reduced melanoma cell growth and induced apoptosis, a cell death pathway distinct from autophagy. Further research is warranted for its potential as an anti-melanoma agent.

Keywords:
Melanomaapoptosisautophagycancercell death.doramectinivermectin

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Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Metastatic melanoma often resists conventional apoptosis-inducing therapies.
  • Alternative cell-death pathways are being explored for melanoma treatment.
  • Doramectin has shown efficacy in neuroblastoma by inhibiting growth via autophagy.

Purpose of the Study:

  • To investigate if doramectin induces autophagy in B16F10 melanoma cells.
  • To explore doramectin's mechanism of action in melanoma.
  • To evaluate doramectin as a potential anti-cancer agent for melanoma.

Main Methods:

  • B16F10 melanoma cells were treated with doramectin.
  • MTT analysis assessed cell viability and growth inhibition.
  • MDC analysis, flow cytometry, and TUNEL assays were used to detect autophagy and cell death.
  • Cells were also treated with a combination of doramectin and a cell-death inhibitor.

Main Results:

  • Doramectin treatment significantly decreased melanoma cell growth.
  • Apoptotic morphology was observed in doramectin-treated cells.
  • Flow cytometry indicated apoptosis and some necrosis as primary cell death mechanisms, not autophagy.
  • MDC analysis did not detect increased autophagy.

Conclusions:

  • Doramectin induces apoptosis and necrosis in melanoma cells, not autophagy.
  • This represents a novel cell-death mechanism for melanoma treatment.
  • Doramectin warrants further investigation as a potential anti-melanoma therapeutic agent.