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

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

Venu Venkatarame Gowda Saralamma, Arulkumar Nagappan, Gyeong Eun Hong, Ho Jeong Lee, Silvia Yumnam, Suchismita Raha, Jeong Doo Heo, Sang Joon Lee, Won Sup Lee, Eun Hee Kim, Gon Sup Kim

Int J Mol Sci. 2015 Sep 18;16(9):22676-91.

PMID: 26393583

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP14941083	Poncirin		14941-08-3	Price

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