Protein bound paclitaxel (Abraxane) mechanism of action. 3D video animations

What is Protein bound paclitaxel (Abraxane) ? Source: National Cancer Institute

protein-bound paclitaxel (PROH-teen… PAK-lih-TAK-sil)
A drug used to treat breast cancer that has spread or that has come back within 6 months after chemotherapy. It is also being studied in the treatment of newly diagnosed breast cancer and other types of cancer. Protein-bound paclitaxel is a type of mitotic inhibitor. Also called ABI-007, Abraxane, nanoparticle paclitaxel, and paclitaxel albumin-stabilized nanoparticle formulation.

Mechanism of action of paclitaxel, from Wikipedia:

Paclitaxel interferes with the normal function of microtubule breakdown. Whereas drugs like colchicine cause the depolymerization of microtubules, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell’s ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the “building block” of microtubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a mechanism to transport other cellular components. For example, during mitosis, microtubules position the chromosomes during their replication and subsequent separation into the two daughter-cell nuclei.

Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.

In addition to stabilizing microtubules paclitaxel may act as a molecular mop by sequestering free tubulin effectively depleting the cells supply of tubulin monomers and/or dimers. This activity may trigger the aforementioned apoptosis.

One common characteristic of most cancer cells is their rapid rate of cell division. In order to accommodate this, the cytoskeleton of a cell undergoes extensive restructuring. Paclitaxel is an effective treatment for aggressive cancers because it adversely affects the process of cell division by preventing this restructuring. Cancer cells are also destroyed by the aforementioned anti-Bcl-2 mechanism. Other cells are also affected adversely, but since cancer cells divide much faster than non-cancerous cells, they are far more susceptible to paclitaxel treatment.

3D video animation of paclitaxel (Taxol) mechanism of action

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