Decoding Mitotic Poisons

Shrestha Sherry Chakraborty, Amity University Kolkata

With the growing instances of cancer worldwide, a common term that we often hear is chemotherapy. Chemotherapy is the most preferred form of cancer treatment worldwide. It is mainly carried out by the use of chemotherapeutics. However, these chemotherapeutics work if not mysterious, but in amazing ways to prevent the growth of malignant cells. This is where mitotic poisons take their entry. Most of the chemotherapeutics are mitotic poisons. Mitotic poisons by definition are chemical agents that kill proliferating cells. Mitotic poisons have been classified under two major categories: The spindle poisons and the Topoisomerase II poisons.

Spindle poisons:

Spindle poisons essentially work on the spindle framework of the cell when the cell is undergoing cell division. The formation of microtubules or spindle fibers is essential in the process of cell division. Some spindle poisons bind to tubulin protein, which can be thought of as monomers. Once bound, they prevent the addition of tubulin to the poles of the cell i.e. the microtubule terminus. Thus, they finally prevent the formation of microtubules.

If the microtubules fail to form, sister chromatids will fail to attach to them and their separation will not occur. Which is a crucial process for cells to divide. On the other hand, some spindle poisons bind to the microtubules and stabilize them. In both instances, a prolonged mitotic arrest is seen which ultimately prevents the cell from diving. 

Topoisomerase poisons:

The second class of mitotic poisons is the topoisomerase poisons also called topo II poisons. Topoisomerase II are enzymes that can cut both strands of DNA double helix and play an important role in the biological processes of recombination, replication, and transcription. When topo II is blocked, it affects the ligation in the cell cycle. Thus creating single and double-stranded breaks in DNA.  These breaks ultimately disrupt the stability of the genome and the cell subsequently undergoes programmed cell death or apoptosis. An example of this type of topo II poison is etoposide.

However,  some topo II poisons also encourage the forward cleavage reaction in DNA. An example of this type of drug is Ciprofloaxin under fluoroquinolones. Topo II poisons have been broadly classified as :

Eukaryotic type II topoisomerase inhibitors- e.g. etoposide and etoposide phosphate among many others and used as chemotherapy drugs worldwide. 

Bacterial type II topoisomerase inhibitors – e.g. Ciprofloaxin works as an antibiotic to treat bacterial infections. 

Thus, these are the many different ways by which mitotic poisons work to prevent malignant cells from dividing and thus prevent the formation of cancer. Thus, they form an important class of chemotherapeutic drugs which are an important part of cancer treatment today. 

Source:

1. Arthur D. Forman, Christina A.Meyers and Victor A. Levin; Neurotoxic Effects of Pharmaceutical Agents IV: Cancer Chemotherapeutic Agents; 2009; Clinical Neurotoxicology; DOI: https://doi.org/10.1016/B978-032305260-3.50039-3

2. Daniel R. Matson and P. Todd Stukenberg; Spindle Poisons and Cell Fate: A Tale of Two Pathways; 2011; Molecular Interventions; 11(2): 141–150; DOI: http://10.1124/mi.11.2.12 URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086919/

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