Question

The bark of the Pacific yew tree (Taxus brevifolia) was the original source of one of the most effective drugs for treating tumors of the breast, lung, and other sites. Taxol, a chemical extracted from this bark, kills actively replicating cells by inhibiting the depolymerization of microtubules. Why are microtubules good targets for killing cancerous cells? During what phases in the cell cycle would you expect there to be large changes in the polymerization or depolymerization of microtubules? Why are these changes necessary?

Short answer

Microtubules are good targets for killing cancerous cells as they play a crucial role in cell division and growth. Taxol inhibits the depolymerization of microtubules, blocking cancerous cells from dividing and spreading. The largest changes in polymerization or depolymerization of microtubules occur during the M phase of the cell cycle, which includes prophase, metaphase, anaphase, and telophase. These changes are vital for proper chromosome alignment, mitotic spindle formation, and chromosome segregation.

Step-by-step solution

Understanding Microtubules

Microtubules are tubular structures that play a crucial role in cell division and growth. They are involved in maintaining the cell's shape, providing proper intracellular transport, and separating the chromosomes during mitosis.

Effects of Taxol on Microtubules

Taxol, a chemical extracted from the bark of the Pacific yew tree (Taxus brevifolia), inhibits the depolymerization of microtubules. This action blocks the cancerous cells from dividing and growing. Since cancer cells typically undergo rapid replication, targeting their microtubule networks with Taxol prevents them from dividing and spreading through the body.

Large Changes in Polymerization or Depolymerization of Microtubules

Significant changes in the polymerization and depolymerization of microtubules occur during the M phase (mitosis) of the cell cycle. This phase includes prophase, metaphase, anaphase, and telophase. These changes are essential for the formation of the mitotic spindle, the proper alignment of chromosomes at the metaphase plate, and the correct separation of the sister chromatids during anaphase.

Importance of Microtubule Changes during the Cell Cycle

Microtubules undergo these necessary changes during the cell cycle to regulate cell division. In prophase, they polymerize to form the mitotic spindle, which aligns chromosomes during metaphase. In anaphase, microtubules depolymerize to shorten the spindle fibers, pulling sister chromatids apart and ensuring their equal distribution into the two daughter cells. These dynamic changes are essential for ensuring proper cell division, maintaining genetic stability, and avoiding chromosomal abnormalities that could lead to cancer or other diseases. In conclusion, microtubules are good targets for killing cancerous cells due to their vital role in cell division and growth. By inhibiting their depolymerization with the drug Taxol, the growth and replication of cancerous cells are hindered. The most significant changes in the polymerization or depolymerization of microtubules occur during the M phase (mitosis) of the cell cycle, and these changes are necessary for proper chromosome alignment, mitotic spindle formation, and chromosome segregation.

Key concepts

Understanding Microtubules

Microtubules are fundamental components of the cell's cytoskeleton, akin to tiny scaffolding within the cell. They consist of tubulin proteins assembled into long, hollow tubes. These structures have multiple roles:

• Maintaining cell shape: Microtubules support the cell's structure, preventing it from collapsing.
• Intracellular transport: They serve as tracks for the movement of organelles and molecules within the cell.
• Chromosome separation: During cell division, microtubules are crucial for moving chromosomes to opposite ends of the cell, a vital process for creating two genetically identical daughter cells.

During the cell cycle, microtubules dynamically assemble and disassemble, especially during mitosis, to help cells divide properly.

The Role of Taxol

Taxol is a potent anti-cancer drug, derived from the bark of the Pacific yew tree. It disrupts the normal functioning of microtubules by preventing their disassembly or depolymerization.

• Blocking Cancer Cell Division: Since cancer cells divide rapidly, Taxol effectively stops them from progressing through cell division.
• Accumulation of Errors: By stabilizing microtubules, Taxol causes defects in the mitotic process, leading to cell death or apoptosis.
• Therapeutic Use: Due to these effects, Taxol is widely used in treating cancers, especially those of the breast, lung, and ovaries, where cell proliferation is aberrant.

Taxol's ability to stabilize microtubules and disrupt cell division makes it a valuable medical tool in cancer therapy.

Microtubules in Mitosis

Mitosis is a short but critical phase in the cell cycle where microtubules are particularly active. The phases of mitosis where microtubules have key roles include:

• Prophase: Microtubules begin to polymerize, forming complexes that will eventually become the mitotic spindle.
• Metaphase: The microtubules align chromosomes on the metaphase plate, ensuring they are correctly positioned for separation.
• Anaphase: Microtubules pull sister chromatids apart toward opposite poles of the cell, a crucial step in ensuring each new cell receives the correct number of chromosomes.
• Telophase: Microtubules start to decompose as the cell prepares to split into two new cells.

The dynamic nature of microtubule assembly and disassembly is fundamental to accurate and equal distribution of genetic material, preventing potential errors that could lead to disease.

Microtubules as Targets in Cancer Therapy

Microtubules make effective targets in cancer therapy due to their critical involvement in cell division. Cancer cells are notorious for their rapid and uncontrolled proliferation. Here’s why targeting microtubules is strategic:

• Essential for Mitosis: Microtubules ensure proper chromosome alignment and segregation, processes that are constantly ongoing in cancer cells.
• Preventing Division: By interfering with microtubule dynamics, drugs like Taxol can halt the division of cancer cells, limiting their spread through the body.
• Minimizing Resistance: Since microtubules are universally involved in cell division, targeting them can be an effective strategy to prevent mutations that lead to drug resistance.

Through drugs that stabilize or destabilize microtubules, cancer treatments aim to exploit the reliance of cancer cells on the robust machinery of mitosis, ultimately leading to their inability to proliferate.