News Column

Kansas State University Reports Findings in Cancer Gene Therapy

June 23, 2014



By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Current study results on Biotechnology have been published. According to news originating from Manhattan, Kansas, by NewsRx correspondents, research stated, "Synthetic 6,7-annulated-4-substituted indole compounds, which elicit interesting antitumor effects in murine L1210 leukemia cells, were tested for their ability to inhibit human HL-60 tumor cell proliferation, disrupt mitosis and cytokinesis, and interfere with tubulin and actin polymerization in vitro. Various markers of metabolic activity, mitotic disruption and cytokinesis were used to assess the effectiveness of the drugs in the HL-60 tumor cell system."

Our news journalists obtained a quote from the research from Kansas State University, "The ability of annulated indoles to alter the polymerizations of purified tubulin and actin were monitored in cell-free assays and were compared to the effects of drugs known to disrupt the dynamic structures of the mitotic spindle and cleavage furrow. With one exception, annulated indoles inhibited the metabolic activity of HL-60 tumor cells in the low-micromolar range after two and four days in culture but these anti-proliferative effects were weaker than those of jasplakinolide, a known actin binder that blocks cytokinesis. After 24-48 h, antiproliferative concentrations of annulated indoles increased the mitotic index of HL-60 cells similarly to vincristine and stimulated the formation of many bi-nucleated cells, multi-nucleated cells and micronuclei, similarly to taxol and jasplakinolide, suggesting that these antitumor compounds might increase mitotic abnormality, induce chromosomal damage or missegregation, and block cytokinesis. Since annulated indoles mimicked the effect of vincristine on tubulin polymerization, but not that of taxol, these compounds might represent a new class of microtubule de-stabilizing agents that inhibit tubulin polymerization. Moreover, annulated indoles remarkably increased the rate and level of actin polymerization similarly to jasplakinolide, suggesting that they might also stabilize the cleavage furrow to block cytokinesis."

According to the news editors, the research concluded: "Although novel derivatives with different substitutions must be synthesized to elucidate structure-activity relationships, identify more potent antitumor compounds and investigate different molecular targets, annulated indoles appear to interact with both tubulin to reduce microtubule assembly and actin to block cytokinesis, thereby inducing bi-and multinucleation, resulting in genomic instability and apoptosis."

For more information on this research see: Mechanisms by which synthetic 6,7-annulated-4-substituted indole compounds with anti-proliferative activity disrupt mitosis and block cytokinesis in human HL-60 tumor cells in vitro. Anticancer Research, 2014;34(4):1643-55. (International Institute of Anticancer Research - www.iiar-anticancer.org/; Anticancer Research - www.iiar-anticancer.org/main.php?id=2)

The news correspondents report that additional information may be obtained from J.P. Perchellet, Anti-Cancer Drug Laboratory, Kansas State University, Division of Biology, Ackert Hall, Manhattan, KS 66506-4901, United States. Additional authors for this research include E.M. Perchellet, C.R. Singh, M.T. Monnett, E.R. Studer, P.D. Thornton, N. Brown, D. Hill, B. Neuenswander, G.H. Lushington, C. Santini and K.R Buszek (see also Biotechnology).

Keywords for this news article include: Biotechnology, Kansas, Tubulin, Manhattan, Cytokines, United States, Microtubule Proteins, Nerve Tissue Proteins, North and Central America.

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Source: Cancer Gene Therapy Week