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

  • Authors:
    • Ho Jeong Lee
    • Arulkumar Nagappan
    • Hyeon Soo Park
    • Gyeong Eun Hong
    • Silvia Yumnam
    • Suchismita Raha
    • Venu Venkatarame Gowda Saralamma
    • Won Sup Lee
    • Eun Hee Kim
    • Gon Sup Kim
  • View Affiliations

  • Published online on: July 10, 2015     https://doi.org/10.3892/or.2015.4122
  • Pages: 1517-1525
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Abstract

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 the molecular mechanism of the anticancer effects of flavonoids isolated from Citrus platymamma (FCP) on AGS cells. FCP treatment significantly inhibited AGS cell growth in a dose‑dependent manner. Furthermore, FCP significantly increased the percentage of cells in the sub-G1 phase (apoptotic cell population), and apoptosis was confirmed by Annexin V double staining. Chromatin condensation and apoptotic bodies were also noted in the FCP-treated AGS cells. Moreover, immunoblotting results showed that FCP treatment significantly decreased the expression of procaspase-3, -6, -8 and -9, and PARP and increased cleaved caspase-3, cleaved PARP and the Bax/Bcl-xL ratio in a dose-dependent manner. In addition, the phosphorylation of AKT was significantly decreased, whereas extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) were significantly increased in the FCP-treated AGS cells. Taken together, the cell death of AGS cells in response to FCP was mitochondrial-dependent via modulation of the PI3K/AKT and MAPK pathways. These findings provide new insight for understanding the mechanism of the anticancer effects of FCP. Thus, FCP may be a potential chemotherapeutic agent for the treatment of gastric cancer.
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September-2015
Volume 34 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lee HJ, Nagappan A, Park HS, Hong GE, Yumnam S, Raha S, Saralamma VV, Lee WS, Kim EH, Kim GS, Kim GS, et al: Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways. Oncol Rep 34: 1517-1525, 2015
APA
Lee, H.J., Nagappan, A., Park, H.S., Hong, G.E., Yumnam, S., Raha, S. ... Kim, G.S. (2015). Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways. Oncology Reports, 34, 1517-1525. https://doi.org/10.3892/or.2015.4122
MLA
Lee, H. J., Nagappan, A., Park, H. S., Hong, G. E., Yumnam, S., Raha, S., Saralamma, V. V., Lee, W. S., Kim, E. H., Kim, G. S."Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways". Oncology Reports 34.3 (2015): 1517-1525.
Chicago
Lee, H. J., Nagappan, A., Park, H. S., Hong, G. E., Yumnam, S., Raha, S., Saralamma, V. V., Lee, W. S., Kim, E. H., Kim, G. S."Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways". Oncology Reports 34, no. 3 (2015): 1517-1525. https://doi.org/10.3892/or.2015.4122