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

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

doi:10.3892/ijo.2015.3095

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
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Affiliations: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea, Gyeongnam Department of Environmental Toxicology and Chemistry, Toxicology Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic of Korea, Department of Nursing Science, International University of Korea, Moonsan, Jinju 660-759, Republic of Korea, Department of Physical Therapy, International University of Korea, Moonsan, Jinju 660-759, Republic of Korea
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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