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Article

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 / Copyright

    Affiliations: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 40402, Taiwan, R.O.C., Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA, Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA
  • Pages: 1596-1606
    |
    Published online on: August 21, 2013
       https://doi.org/10.3892/ijo.2013.2069
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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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Copy and paste a formatted citation
Spandidos Publications style
Lin Y, Tsai J, Yang J, Lee Y, Hamel E, Lee K, Kuo S and 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. Int J Oncol 43: 1596-1606, 2013.
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
Copy and paste a formatted citation
x
Spandidos Publications style
Lin Y, Tsai J, Yang J, Lee Y, Hamel E, Lee K, Kuo S and 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. Int J Oncol 43: 1596-1606, 2013.
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
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