Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways.

作者: HO JEONG LEE , ARULKUMAR NAGAPPAN , HYEON SOO PARK , GYEONG EUN HONG , SILVIA YUMNAM

DOI: 10.3892/OR.2015.4122

关键词: PI3K/AKT/mTOR pathwayProtein kinase BMAPK/ERK pathwayp38 mitogen-activated protein kinasesBiologyCell biologyApoptosisProgrammed cell deathKinaseCell growth

摘要: Citrus platymamma hort. ex Tanaka (Rutaceae family) has been widely used in Korean folk medicine for its wide range of medicinal benefits including an anticancer effect. In the present study, we aimed to investigate molecular mechanism effects flavonoids isolated from (FCP) on AGS cells. FCP treatment significantly inhibited cell growth a dose‑dependent manner. Furthermore, increased percentage cells sub-G1 phase (apoptotic population), and apoptosis was confirmed by Annexin V double staining. Chromatin condensation apoptotic bodies were also noted FCP-treated Moreover, immunoblotting results showed that decreased expression procaspase-3, -6, -8 -9, PARP cleaved caspase-3, Bax/Bcl-xL ratio dose-dependent addition, phosphorylation AKT decreased, whereas extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs) Taken together, death response mitochondrial-dependent via modulation PI3K/AKT MAPK pathways. These findings provide new insight understanding FCP. Thus, may be potential chemotherapeutic agent gastric cancer.

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