The novel synthetic compound 6-acetyl-9-(3,4,5-trimetho­xybenzyl)-9H-pyrido[2,3-b]indole induces mitotic arrest and apoptosis in human COLO 205 cells

  • Authors:
    • Yi-Chien Lin
    • Jui-Ying Tsai
    • Jai-Sing Yang
    • Yueh-Hsuan Lee
    • Ernest Hamel
    • Kuo-Hsiung Lee
    • Sheng-Chu Kuo
    • Li-Jiau Huang
  • View Affiliations

  • Published online on: August 21, 2013     https://doi.org/10.3892/ijo.2013.2069
  • Pages: 1596-1606
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Abstract

A novel synthetic compound 6-acetyl-9-(3,4,5-trimetho­xybenzyl)-9H-pyrido[2,3-b]indole (HAC-Y6) demonstrated selective anticancer activity. In the present study, COLO 205 cells were treated with HAC-Y6 to investigate the molecular mechanisms underlying its effects. HAC-Y6 induced growth inhibition, G2/M arrest and apoptosis in COLO 205 cells with an IC50 of 0.52±0.035 µM. Annexin V/PI double staining demonstrated the presence of apoptotic cells. JC-1 staining analysis showed that HAC-Y6 decreased mitochondrial membrane potential in support of apoptosis. An immunostaining assay revealed that HAC-Y6 depolymerized microtubules. Treatment of COLO 205 cells with HAC-Y6 resulted in increased expression of BubR1 and cyclin B1 and decreased expression of aurora A, phospho-aurora A, aurora B, phospho‑aurora B and phospho-H3. HAC-Y6 treatment increased protein levels of active caspase-3, caspase-9, Endo G, AIF, Apaf-1, cytochrome c and Bax, but treatment with the compound caused reduced levels of procaspase-3, procaspase-9, Bcl-xL and Bcl-2. Overall, our results suggest that HAC-Y6 exerts anticancer effects by disrupting microtubule assembly and inducing G2/M arrest, polyploidy and apoptosis via mitochondrial pathways in COLO 205 cells.
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November 2013
Volume 43 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Lin, Y., Tsai, J., Yang, J., Lee, Y., Hamel, E., Lee, K. ... Huang, L. (2013). The novel synthetic compound 6-acetyl-9-(3,4,5-trimetho­xybenzyl)-9H-pyrido[2,3-b]indole induces mitotic arrest and apoptosis in human COLO 205 cells. International Journal of Oncology, 43, 1596-1606. https://doi.org/10.3892/ijo.2013.2069
MLA
Lin, Y., Tsai, J., Yang, J., Lee, Y., Hamel, E., Lee, K., Kuo, S., Huang, L."The novel synthetic compound 6-acetyl-9-(3,4,5-trimetho­xybenzyl)-9H-pyrido[2,3-b]indole induces mitotic arrest and apoptosis in human COLO 205 cells". International Journal of Oncology 43.5 (2013): 1596-1606.
Chicago
Lin, Y., Tsai, J., Yang, J., Lee, Y., Hamel, E., Lee, K., Kuo, S., Huang, L."The novel synthetic compound 6-acetyl-9-(3,4,5-trimetho­xybenzyl)-9H-pyrido[2,3-b]indole induces mitotic arrest and apoptosis in human COLO 205 cells". International Journal of Oncology 43, no. 5 (2013): 1596-1606. https://doi.org/10.3892/ijo.2013.2069