What is 12-o-tetradecanoyl phorbol-13-acetate?

12-O-Tetradecanoylphorbol-13-Acetate (TPA)

12-O-Tetradecanoylphorbol-13-acetate (TPA), also known as phorbol-12-myristate-13-acetate (PMA), is a diester of phorbol and a potent tumor promoter. It is frequently used in biological research, particularly in studies of signal transduction, cell proliferation, and inflammation.

• Mechanism of Action: TPA is a potent activator of <a href="https://www.wikiwhat.page/kavramlar/protein%20kinase%20C">Protein Kinase C (PKC)</a>. It binds to PKC with high affinity, mimicking the endogenous activator diacylglycerol (DAG). Prolonged activation of PKC by TPA can lead to various cellular effects, including changes in gene expression, cell growth, differentiation, and apoptosis.

• Tumor Promotion: TPA is a classical example of a tumor promoter. It does not directly cause DNA mutations (initiation), but it enhances the development of tumors in cells that have already undergone initiation. It promotes clonal expansion of initiated cells leading to tumor development.

• Applications in Research: Due to its potent effects on cell signaling, TPA is widely used in various research areas:

  • Cellular Differentiation: TPA can induce differentiation in certain cell types, such as HL-60 leukemia cells into macrophage-like cells.
  • Inflammation: TPA can stimulate inflammatory responses by activating immune cells.
  • Signal Transduction: It's a valuable tool for studying PKC-mediated signaling pathways.
  • Gene Expression: TPA can alter gene expression patterns by activating transcription factors like <a href="https://www.wikiwhat.page/kavramlar/NF-κB">NF-κB</a>.

• Toxicity and Safety: TPA is a potent and toxic compound. It should be handled with extreme care in a laboratory setting. Contact with skin and eyes should be avoided, and appropriate personal protective equipment should be used.

• Chemical Properties: TPA is typically supplied as a solid. It is soluble in organic solvents such as DMSO and ethanol. Aqueous solutions are unstable, and degradation can occur, especially at alkaline pH.