Microtubules and Cell Division: Potential Pharmacological Targets in Cancer Therapy

Abstract

Microtubules are a well-known target in cancer chemotherapy because of their critical role in cell division. Chromosome segregation during mitosis depends on the establishment of the mitotic spindle apparatus through microtubule dynamics. The disruption of microtubule dynamics through the stabilization or destabilization of microtubules results in the mitotic arrest of the cells. Microtubule-targeted drugs, which interfere with microtubule dynamics, inhibit the growth of cells at the mitotic phase and induce apoptotic cell death. The principle of microtubule-targeted drugs is to arrest the cells at mitosis and reduce their growth because cancer is a disease of unchecked cell proliferation. Many anti-microtubule agents produce significant inhibition of cancer cell growth and are widely used as chemotherapeutic drugs for the treatment of cancer. The drugs that interact with microtubules generally bind at one of the three sites vinblastine site, taxol site, or colchicine site. Colchicine binds to the interface of tubulin heterodimer and induces the depolymerization of microtubules. The colchicine binding site on microtubules is a much sought-after target in the history of anti-microtubule drug discovery. Many colchicine-binding site inhibitors have been discovered, but their use in the treatment of cancer is limited due to their dose-limiting toxicity and resistance in humans. Combination therapy can be a new treatment strategy to overcome these drawbacks of currently available microtubule-targeted anticancer drugs. This review discusses the significance of microtubules as a potential pharmacological target for cancer and stresses the necessity of finding new microtubule inhibitors to fight the disease.

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

“…Secondly, we found that BC patients had lower IC50 and greater drug molecule affinity for docetaxel, paclitaxel and vinblastine in the high KCNK1 expression group. The three drugs mentioned above were reported to work by blocking the progression of the cell cycle, which ultimately led to the death of the cancer cells [ 51 , 52 ]. Paclitaxel and docetaxel might affect the proliferation of BRCA cells by modulating potassium currents, and TME could induce docetaxel resistance [ 42 , 53 , 54 ].…”

Design, synthesis and cytotoxic activity of molecular hybrids based on quinolin-8-yloxy and cinnamide hybrids and their apoptosis inducing property

“…Microtubules play a vital role in the movement of chromosomes during cellular division. 35 As most tubulin destabilized agents disrupted the regulated cellular cycle distribution, flow cytometric analysis was performed to determine the impact of quinoline-4-methoxycinnamide hybrid 6e on the HepG2 cell cycle. The cancerous cells were treated with the tested compounds at 2.46 μM and control for 48 h. As illustrated in Fig.…”

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD

“… 25 - 27 Hence, targeting microtubule (MT) dynamics to disrupt mitotic spindle assembly and reduce chromosomal separation and chromosomal instability (CIN) during mitosis in lung cancer cells has been widely employed as a therapeutic strategy using chemotherapy drugs in cancer treatment. 28 Previous research has demonstrated that during mitosis, Aurora A kinase facilitates microtubule (MT) nucleation around chromatin through the phosphorylation of NEDD1. This phosphorylation event promotes the proper assembly of a functional mitotic spindle.…”

“… 39 Paclitaxel, or docetaxel, which act on the microtubule paclitaxel site, cause mitosis arrest of cells by destroying the microtubule network, but it is also believed that paclitaxel exerts its anti-cancer effect by causing chromosomal malfusion on the multipolar spindle of cancer cells, increasing chromosomal instability. 28 , 40 Cisplatin plus pemetrexed, paclitaxel, or docetaxel is the first-line treatment of choice in driver-negative cases of advanced LUAD. Crizotinib is recommended for patients with positive ALK and ROS1 fusion genes, but unfortunately our results did not show a correlation between NEDD1 and other driver genes.…”