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Review
. 2018 Dec 10;73(suppl 1):e813s.
doi: 10.6061/clinics/2018/e813s.

Natural Products as New Antimitotic Compounds for Anticancer Drug Development

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Free PMC article
Review

Natural Products as New Antimitotic Compounds for Anticancer Drug Development

Carlos Roberto Koscky Paier et al. Clinics (Sao Paulo). .
Free PMC article

Abstract

Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide. However, severe adverse effects such as neuropathies are frequently observed during treatment with microtubule-targeting agents. Many efforts have been directed at developing improved antimitotics with increased specificity and decreased likelihood of inducing side effects. These new drugs generally target specific components of mitotic regulation that are mainly or exclusively expressed during cell division, such as kinases, motor proteins and multiprotein complexes. Such small molecules are now in preclinical studies and clinical trials, and many are products or derivatives from natural sources. In this review, we focused on the most promising targets for the development of antimitotics and discussed the advantages and disadvantages of these targets. We also highlighted the novel natural antimitotic agents under investigation by our research group, including combretastatins, withanolides and pterocarpans, which show the potential to circumvent the main issues in antimitotic therapy.

Conflict of interest statement

No potential conflict of interest was reported.

Figures

Figure 1
Figure 1
Antimitotic targets and their respective inhibitors as cited in the text. The targets are placed in the illustration according to the cell cycle phase in which they perform their main functions. The corresponding inhibitors are listed in the legend. The phases of mitosis are depicted in blue, the phases of interphase are in green, and cell cycle checkpoints are in red. The compounds (+)2,3,9-trimethoxypterocarpan and withaphysalin F are not included, because their targets are unknown.
Figure 2
Figure 2
Combretastatin A-4 analogs. (A) LASSBio-1586. (B) LASSBio-1920.
Figure 3
Figure 3
Structure of pterocarpans isolated from Platymiscium floribundum by Falcão et al. .
Figure 4
Figure 4
Formation of atypical mitotic spindles in 2,3,9-trimethoxypterocarpan-treated cells. Actin (green), tubulin (blue) and nuclei (red) are labeled in breast carcinoma and nontumor (BRL3A) cells treated or not treated with the compound. Note the normal arrangement of tubulin and actin fibers in the control cells; the formation of monopolar spindles in MCF-7, HS58T and BRL3A cells; and the formation of tripolar spindles in T47D cells. Figure from Militão et al. .

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References

    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144((5)):646–74. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9((3)):153–66. doi: 10.1038/nrc2602. - DOI - PubMed
    1. Marzo I, Naval J. Antimitotic drugs in cancer chemotherapy: promises and pitfalls. Biochem Pharmacol. 2013;86((6)):703–10. doi: 10.1016/j.bcp.2013.07.010. - DOI - PubMed
    1. Sudakin V, Yen TJ. Targeting mitosis for anti-cancer therapy. BioDrugs. 2007;21((4)):225–33. doi: 10.2165/00063030-200721040-00003. - DOI - PubMed
    1. Penna LS, Henriques JAP, Bonatto D. Anti-mitotic agents: are they emerging molecules for cancer treatment? Pharmacol Ther. 2017;173:67–82. doi: 10.1016/j.pharmthera.2017.02.007. - DOI - PubMed

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