Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

International Journal of Molecular Sciences

Venu Venkatarame Gowda Saralamma³  Arulkumar Nagappan⁴  Gyeong Eun Hong³  Ho Jeong Lee³  Silvia Yumnam³  Suchismita Raha³  Jeong Doo Heo¹  Sang Joon Lee¹  Won Sup Lee⁴  Eun Hee Kim²  Gon Sup Kim³ 

[1] Gyeongnam Department of Environment Toxicology and Chemistry, Toxicity Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Korea; E-Mails:;Department of Nursing Science, International University of Korea, Jinju 660-759, Korea; E-Mail:;Research Institute of Life Science and College of Veterinary Medicine (BK21 Plus Project), Gyeongsang National University, Gazwa, Jinju 660-701, Korea; E-Mails:;Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea; E-Mails:

关键词: Poncirin;    gastric adenocarcinoma;    AGS cells;    FasL;    caspases;    apoptosis;   

DOI  :  10.3390/ijms160922676

来源: mdpi

【 摘 要 】

Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

【 授权许可】

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