Mitotic Poisons in Research and Medicine

Abstract

Cancer is one of the greatest challenges of the modern medicine. Although much effort has been made in the development of novel cancer therapeutics, it still remains one of the most common causes of human death in the world, mainly in low and middle-income countries. According to the World Health Organization (WHO), cancer treatment services are not available in more then 70% of low-income countries (90% of high-income countries have them available), and also approximately 70% of cancer deaths are reported in low-income countries. Various approaches on how to combat cancer diseases have since been described, targeting cell division being among them. The so-called mitotic poisons are one of the cornerstones in cancer therapies. The idea that cancer cells usually divide almost uncontrolled and far more rapidly than normal cells have led us to think about such compounds that would take advantage of this difference and target the division of such cells. Many groups of such compounds with different modes of action have been reported so far. In this review article, the main approaches on how to target cancer cell mitosis are described, involving microtubule inhibition, targeting aurora and polo-like kinases and kinesins inhibition. The main representatives of all groups of compounds are discussed and attention has also been paid to the presence and future of the clinical use of these compounds as well as their novel derivatives, reviewing the finished and ongoing clinical trials.

Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity

“…Thus, even though further elaboration in deciphering detailed mechanisms of Hyr and deHyr and other CG anticancer activity is needed, the first results already indicate that these CGs could have a potential for a therapeutic application in cancer treatment. From the number of publications on CGs as anticancer drugs, it is obvious that they have come into the foreground as candidates of anticancer therapy with new mechanisms of actions than the standardly used chemotherapeutics, such as antimitotics [ 60 ] or cisplatin, and that their induction of the immune system response brings another added value in the treatment. We assume that our results can contribute to further development of drugs based on NKA interaction, and maybe additional molecular targets with selective cytotoxicity for cancer cells.…”

Current Perspectives on Taxanes: Focus on Their Bioactivity, Delivery and Combination Therapy

“…Mitotic poisons do not generally target only microtubules, as taxanes do, but they target also other proteins playing an essential role in cancer, i.e., aurora and polo-like kinases and kinesins, summarized in ref. [ 191 ]. A combination of antimitotic drugs that proceeded already to clinical trials (five completed, one inactive phase), is paclitaxel co-administered with an inhibitor of aurora kinase A, alisertib [ 192 ].…”

Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential

“…Natural products have played an important role in treating a variety of diseases [10][11][12]. Among them, many anti-cancer drugs currently used clinically are derived from plants or are derivatives of natural products [13][14][15].…”