Open Access

5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle

  • Authors:
    • Natasha Borah
    • Shimara Gunawardana
    • Haydee Torres
    • Susan McDonnell
    • Severine Van Slambrouck
  • View Affiliations

  • Published online on: October 13, 2017     https://doi.org/10.3892/ijo.2017.4157
  • Pages:1685-1693
  • Copyright: © Borah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Natural components continue to be an important source for the discovery and development of novel anticancer agents. Polymethoxyflavones are a class of flavonoids found in citrus fruits and medicinal plants used in traditional medicine. In the present study, the anticancer activity of the well-known nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) was compared against its less studied structural isomer 5,6,7,3',4',5'-hexamethoxyflavone. These compounds were evaluated on the Hs578T triple-negative breast cancer cell line and its more migratory subclone Hs578Ts(i)8. 5,6,7,3',4',5'-hexamethoxyflavone was found to be less toxic than nobiletin, while a similar growth inhibitory effect was observed after 72 h. Additionally, 5,6,7,3',4',5'-hexamethoxyflavone arrested the cell cycle in the G2/M phase, while no effect was observed on apoptosis or the migratory behavior of these cells. Furthermore, mechanistic studies revealed that the growth inhibition was concomitant with reduced phosphorylation levels of signaling molecules in the MAPK and Akt pathways as well as cell cycle regulators, involved in regulating cell proliferation, survival and cell cycle. In summary, the present study is the first to report on the anticancer activities of 5,6,7,3',4',5'-hexamethoxyflavone and to provide evidence that this flavone could have a greater potential than nobiletin for prevention or treatment of triple- negative breast cancer.

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December 2017
Volume 51 Issue 6

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

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APA
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., & Van Slambrouck, S. (2017). 5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle. International Journal of Oncology, 51, 1685-1693. https://doi.org/10.3892/ijo.2017.4157
MLA
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., Van Slambrouck, S."5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle". International Journal of Oncology 51.6 (2017): 1685-1693.
Chicago
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., Van Slambrouck, S."5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle". International Journal of Oncology 51, no. 6 (2017): 1685-1693. https://doi.org/10.3892/ijo.2017.4157