From the Guidelines
Paclitaxel works primarily by stabilizing microtubules during cell division, binding specifically to the beta-tubulin subunit of microtubules, preventing their disassembly and creating extremely stable, non-functional microtubules, which ultimately leads to apoptosis (programmed cell death) in cancer cells. This mechanism of action makes paclitaxel effective against rapidly dividing cells, particularly cancer cells in solid tumors such as breast, ovarian, lung, and other cancers 1. The drug is typically administered intravenously, with dosing regimens varying by cancer type and treatment protocol.
Key Points about Paclitaxel's Mechanism of Action:
- Paclitaxel stabilizes microtubules, preventing their disassembly and creating non-functional microtubules.
- It binds specifically to the beta-tubulin subunit of microtubules.
- This disrupts the normal dynamic reorganization of the microtubule network needed for mitosis and cell division.
- Paclitaxel causes the mitotic spindle to malfunction, triggering cell cycle arrest in the G2/M phase and ultimately leading to apoptosis.
- Unlike other antimicrotubule agents, paclitaxel promotes assembly and prevents depolymerization of microtubules.
Administration and Side Effects:
- Paclitaxel is administered intravenously.
- Dosing regimens vary by cancer type and treatment protocol.
- Side effects result from paclitaxel's action on normal dividing cells and include neutropenia, peripheral neuropathy, and hypersensitivity reactions 1.
Clinical Use:
- Paclitaxel is used in the treatment of various cancers, including breast, ovarian, lung, and other solid tumors.
- It is often used in combination with other chemotherapy agents, such as carboplatin 1.
- The choice of treatment and dosing regimen depends on the specific cancer type, stage, and patient characteristics.
From the FDA Drug Label
Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
The mechanism of action of paclitaxel is to promote the assembly of microtubules and stabilize them by preventing depolymerization, which inhibits the normal dynamic reorganization of the microtubule network essential for cellular functions. This leads to the inhibition of cell division and ultimately cell death. 2
From the Research
Mechanism of Action of Paclitaxel
The mechanism of action of paclitaxel involves several key processes:
- Microtubule stabilization: Paclitaxel binds to microtubules and causes kinetic suppression (stabilization) of microtubule dynamics, leading to cell cycle arrest at the mitotic phase 3.
- Induction of apoptosis: Paclitaxel induces apoptosis in cancer cells through multiple mechanisms, including activation of signaling molecules, transcriptional activation of various genes, and involvement of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway 3.
- Antiangiogenic activity: Paclitaxel alters cytoskeletal structure, affecting migration and invasion, and has antiangiogenic activity 4.
- Cell cycle arrest: Paclitaxel causes cell cycle arrest at the mitotic phase, leading to cell death in a subset of the arrested population 5.
Key Effects of Paclitaxel
Some key effects of paclitaxel include:
- Inhibition of cell growth: Paclitaxel inhibits cell growth and induces cell death in cancer cells 4, 6.
- Induction of multipolar divisions: Low concentrations of paclitaxel can cause multipolar divisions instead of mitotic arrest 5.
- Treatment of various cancers: Paclitaxel is used to treat a range of cancers, including breast, lung, and ovarian cancer, as well as Kaposi's sarcoma 6, 5.
- Potential uses in non-cancer diseases: Paclitaxel may have potential uses in treating non-cancer diseases, such as skin disorders, renal and hepatic fibrosis, and inflammation 7.