Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells

  • Authors:
    • Suchismita Raha
    • Silvia Yumnam
    • Gyeong Eun Hong
    • Ho Jeong Lee
    • Venu Venkatarame Gowda Saralamma
    • Hyeon-Soo Park
    • Jeong Doo Heo
    • Sang Joon Lee
    • Eun Hee Kim
    • Jin-A Kim
    • Gon Sup Kim
  • View Affiliations

  • Published online on: July 20, 2015     https://doi.org/10.3892/ijo.2015.3095
  • Pages: 1061-1069
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Abstract

Naringin, one of the major bioflavonoid of Citrus, has been demonstrated as potential anticancer agent. However, the underlying anticancer mechanism still needs to be explored further. This study investigated the inhibitory effect of Naringin on human AGS cancer cells. AGS cell proliferation was inhibited by Naringin in a dose- and time-dependent manner. Naringin did not induce apoptotic cell death, determined by no DNA fragmentation and the reduced Bax/Bcl-xL ratio. Growth inhibitory role of Naringin was observed by western blot analysis demonstrating downregulation of PI3K/Akt/mTOR cascade with an upregulated p21CIPI/WAFI. Formation of cytoplasmic vacuoles and autophagosomes were observed in Naringin-treated AGS cells, further confirmed by the activation of autophagic proteins Beclin 1 and LC3B with a significant phosphorylation of mitogen activated protein kinases (MAPKs). Collectively, our observed results determined that anti-proliferative activity of Naringin in AGS cancer cells is due to suppression of PI3K/Akt/mTOR cascade via induction of autophagy with activated MAPKs. Thus, the present finding suggests that Naringin induced autophagy- mediated growth inhibition shows potential as an alternative therapeutic agent for human gastric carcinoma.
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September 2015
Volume 47 Issue 3

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

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APA
Raha, S., Yumnam, S., Hong, G.E., Lee, H.J., Saralamma, V.V., Park, H. ... Kim, G.S. (2015). Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells. International Journal of Oncology, 47, 1061-1069. https://doi.org/10.3892/ijo.2015.3095
MLA
Raha, S., Yumnam, S., Hong, G. E., Lee, H. J., Saralamma, V. V., Park, H., Heo, J. D., Lee, S. J., Kim, E. H., Kim, J., Kim, G. S."Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells". International Journal of Oncology 47.3 (2015): 1061-1069.
Chicago
Raha, S., Yumnam, S., Hong, G. E., Lee, H. J., Saralamma, V. V., Park, H., Heo, J. D., Lee, S. J., Kim, E. H., Kim, J., Kim, G. S."Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells". International Journal of Oncology 47, no. 3 (2015): 1061-1069. https://doi.org/10.3892/ijo.2015.3095