The drugs taxol, extracted from the bark of yew trees, and colchicines, an alkal

Question

The drugs taxol, extracted from the bark of yew trees, and colchicines, an alkaloid from autumn crocus, have opposite effects. Taxol binds tightly to microtbules and stabilizes them. When added to cell, it causes much of the free tubulin to assemble into microtubules. In contrast, colchicine prevents microtubule formation. Taxol and colchicine are equally toxic and dividing cells, and both are used as anticancer drugs. Based on your knowledge of microtubule dynamics, explain why these drugs are toxic to dividing cells despite their opposite modes of action?

Explanation / Answer

This is a great question since it involves poisons and cell bio!

Cells undergoing mitosis and meiosis (with cancer it's mitosis you have to think about) require a precise sequence of interphase + the mitotic steps of prophase-metaphase-anaphase-telophase before cytokinesis can occur. This goes on in the human body countless times every day. Every time you exfoliate in the shower, thousands of cells slough off and the layer of skin beneath actively replaces them. Similarly, blood and immune cells are constantly replaced through synthesis in bone marrow.

However, cancer cells undergo uncontrolled mitosis and have shorter lifespans as a result of many genetic changes. So mitosis is a useful target to prevent these cells from reproducing, after which the remaining cells will more quickly die out. Basically, cancer cells are more sensitive to mitosis-blocking agents.

In the case of both taxol & colchicines, both of these drugs prevent the proper formation of mitotic spindles, which prevents the progression of mitosis. Proper mitosis requires that a mitotic spindle be formed out of assembled microtubules and linked together + linked to each chromosome through specialized kinetochore microtubules.

Taxol = causes free tubulin (building block of microtubules) to permanently assemble into MT's which are not associated with the mitotic spindle, preventing mitosis from progressing

Colchicines = impedes any microtubule formation so a spindle simply can't form

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