Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress

  • Authors:
    • Yoon-Mi Lee
    • Gibok Lee
    • Taek-In Oh
    • Byeong Mo Kim
    • Do-Wan Shim
    • Kwang-Ho Lee
    • Young Jun Kim
    • Beong Ou Lim
    • Ji-Hong Lim
  • View Affiliations

  • Published online on: November 11, 2015     https://doi.org/10.3892/ijo.2015.3243
  • Pages: 399-408
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Abstract

Recent studies have shown anticancer activity of apigenin by suppressing glucose transporter 1 (GLUT1) expression in cultured cancer cells; however, it is not clear whether apigenin can suppress glucose metabolism in lung cancer cells or sensitize them to inhibition of glutamine utilization-mediated apoptosis through metabolic and oxidative stress. We show that apigenin significantly decreases GLUT1 expression in mice. Furthermore, we demonstrate that apigenin induces growth retardation and apoptosis through metabolic and oxidative stress caused by suppression of glucose utilization in lung cancer cells. The underlying mechanisms were defined that the anticancer effects of apigenin were reversed by ectopic GLUT1 overexpression and galactose supplementation, through activation of pentose phosphate pathway-mediated NADPH generation. Importantly, we showed that severe metabolic stress using a glutaminase inhibitor, compound 968, was involved in the mechanism of sensitization by apigenin. Taken together, the combination of apigenin with inhibitors of glutamine metabolism may provide a promising therapeutic strategy for cancer treatment.
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January-2016
Volume 48 Issue 1

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

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Spandidos Publications style
Lee Y, Lee G, Oh T, Kim BM, Shim D, Lee K, Kim YJ, Lim BO and Lim J: Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress. Int J Oncol 48: 399-408, 2016
APA
Lee, Y., Lee, G., Oh, T., Kim, B.M., Shim, D., Lee, K. ... Lim, J. (2016). Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress. International Journal of Oncology, 48, 399-408. https://doi.org/10.3892/ijo.2015.3243
MLA
Lee, Y., Lee, G., Oh, T., Kim, B. M., Shim, D., Lee, K., Kim, Y. J., Lim, B. O., Lim, J."Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress". International Journal of Oncology 48.1 (2016): 399-408.
Chicago
Lee, Y., Lee, G., Oh, T., Kim, B. M., Shim, D., Lee, K., Kim, Y. J., Lim, B. O., Lim, J."Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress". International Journal of Oncology 48, no. 1 (2016): 399-408. https://doi.org/10.3892/ijo.2015.3243