Title:Cell Cycle Arrest and Apoptosis Induction of Phloroacetophenone Glycosides and Caffeoylquinic Acid Derivatives in Gastric Adenocarcinoma (AGS) Cells
VOLUME: 18 ISSUE: 4
Author(s):Naser Jafari, Seyed Jalal Zargar*, Mohammad-Reza Delnavazi and Narguess Yassa
Affiliation:Department of Cell & Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Department of Cell & Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran
Keywords:Caffeoylquinic acid, phloroacetophenone glycosides, gastric cancer, apoptosis, cell cycle.
Abstract:Introduction: In the present study, we analyzed anti-proliferative and apoptosis induction activity of
five phenolic compounds: echisoside, pleoside, chlorogenic acid, 4,5-Di-O-caffeoylquinic acid, and cynarin on
AGS (adenocarcinoma gastric) cell line.
Method: These phenolic compounds were isolated from methanol extract of Dorema glabrum root. An MTT
assay was conducted to evaluate the inhibitory effect on cancer cells. EB/AO staining was done to assess the
mode of cell death and morphological changes of the cells’ nuclei. Cell cycle distribution of the cells was analyzed
by flow cytometry, and for further confirmation of the pathway, mRNA levels of apoptosis cascade players
were quantified by qRT-PCR.
Result: We found that echisoside, pleoside, chlorogenic acid, 4,5-Di-O-caffeoylquinic acid, and cynarin inhibited
the proliferation of AGS cancer cells in vitro. Our data revealed that these compounds triggered morphological
changes characteristic of apoptotic cell death. These compounds up-regulated bax and caspase3 expression
and down-regulated cyclin D1, bcl2, VEGFA, c-myc and survivin. Moreover, cell population increased at
the G1 phase, and a number of cells at the G2/M phase of the cell cycle decreased after treatment.
Conclusion: All these data suggest that phenolic compounds have a cytotoxic effect on gastric cancer cells and
could trigger apoptosis. Besides cytotoxic activity, they could potentially arrest the cell cycle at the G1 phase.
