Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cellsopen access
- Authors
- 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
- Issue Date
- Sep-2015
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- naringin; gastric carcinoma; AGS cells; growth inhibition; autophagy; MAPKs
- Citation
- INTERNATIONAL JOURNAL OF ONCOLOGY, v.47, no.3, pp.1061 - 1069
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF ONCOLOGY
- Volume
- 47
- Number
- 3
- Start Page
- 1061
- End Page
- 1069
- URI
- https://scholarworks.bwise.kr/gnu/handle/sw.gnu/17046
- DOI
- 10.3892/ijo.2015.3095
- ISSN
- 1019-6439
- 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 p21(CIPI/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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