Abstract
Purpose: To investigate the effect of apigenin on Barrett's esophagus–associated esophageal adenocarcinoma (BEAC) cells OE33, and also to ascertain the mechanism by which it inhibits cellular proliferation and motility. Methods: Proliferation index of OE33 in the absence and presence of apigenin was determined by methyl-thiazolyl-tetrazolium (MTT) assay and apoptosis was determined by enzyme-linked immunosorbent assay (ELISA) method. Boyden Chamber’s assay was applied to determine the migration and invasion of control and apigenin-treated OE33 cells. Status of PI3K/Akt/mTor signaling was further determined by Western blotting in control and apigenin-treated cells. Results: Apigenin resulted in the inhibition of the proliferation of OE33 cells in a dose- and timedependent fashion, with an IC 50 of 75 μM, after 72 h of incubation, and also induced apoptosis, with modulation of pro- and anti-apoptotic genes. Furthermore, apigenin inhibited the motility of OE33 by targeting PI3K/Akt/mTOR signaling. Conclusion: Apigenin effectively inhibits the oncogenicity of OE33 cells by targeting PI3K/Akt/mTOR pathway. Keywords: Barrett's esophagus–associated esophageal adenocarcinoma (BEAC), Apoptosis, Migration, Anticancer
Highlights
Apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl)4H-1-benzo-pyran-4-one] is a dietary flavone, found abundantly in fruits and variety of vegetables including parsley, oranges, onions, tea, chamomile, wheat sprouts, etc [1,2]
In the United States alone, the incidence of Barrett's esophagus–associated esophageal adenocarcinoma (BEAC) had increased by 300 % to 500 % in the last 40 years [17] and recently published meta-analysis studies reveal that similar risk factors of Barrett's esophagus prevail in Asian countries [18]
Barrett’s esophagus (BE) is known to be the most significant precursor lesion for esophageal adenocarcinoma (EAC) [19], which resulted from the longstanding exposure of the esophageal mucosa to gastro-esophageal reflux, resulting in the metaplastic replacement of the native squamous epithelia by columnar cells (i.e. Barrett’s mucosa) [20,21]
Summary
Apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl)4H-1-benzo-pyran-4-one] is a dietary flavone, found abundantly in fruits and variety of vegetables including parsley, oranges , onions, tea, chamomile, wheat sprouts, etc [1,2]. Barrett’s esophagus (BE) is known to be the most significant precursor lesion for esophageal adenocarcinoma (EAC) [19], which resulted from the longstanding exposure of the esophageal mucosa to gastro-esophageal reflux, resulting in the metaplastic replacement of the native squamous epithelia by columnar cells (i.e. Barrett’s mucosa) [20,21]. This epithelial population serves as the platform for the formation of intra-epithelial neoplasia, termed as dysplasia, which thereafter might lead to the Barrett-related EAC [20,21].
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