title: Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells.
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.
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Raha
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Silvia
authors.initials: S
authors.lastname: Yumnam
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Gyeong Eun
authors.initials: GE
authors.lastname: Hong
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Venu Venkatarame Gowda
authors.initials: VV
authors.lastname: Saralamma
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Gyeongnam Department of Environmental Toxicology and Chemistry, Toxicology Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic of Korea.
authors.forename: Jeong Doo
authors.initials: JD
authors.lastname: Heo
authors.affiliation: Gyeongnam Department of Environmental Toxicology and Chemistry, Toxicology Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Nursing Science, International University of Korea, Moonsan, Jinju 660-759, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Physical Therapy, International University of Korea, Moonsan, Jinju 660-759, Republic of Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C005274:naringin