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8‐ C ‐( E ‐phenylethenyl)quercetin from onion/beef soup induces autophagic cell death in colon cancer cells through ERK activation
Author(s) -
Zhao Yueliang,
Fan Daming,
Zheng ZongPing,
Li Edmund T.S.,
Chen Feng,
Cheng KaWing,
Wang Mingfu
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600437
Subject(s) - mapk/erk pathway , programmed cell death , viability assay , kinase , apoptosis , cell growth , protein kinase a , chemistry , autophagy , flow cytometry , quercetin , cancer cell , microbiology and biotechnology , cancer research , biochemistry , biology , cancer , antioxidant , genetics
Scope Quercetin, a flavonoid, widely distributed in edible fruits and vegetables, was reported to effectively inhibit 2‐amino‐1‐methyl‐6‐phenylimidazo[4, 5‐b]pyridine (PhIP) formation in a food model (roast beef patties) with itself being converted into a novel compound 8‐ C ‐( E ‐phenylethenyl)quercetin (8‐ CEPQ ). Here we investigated whether 8‐ CEPQ could be formed in a real food system, and tested its anticancer activity in human colon cancer cell lines. Methods and results LC‐MS was applied for the determination of 8‐ CEPQ formation in onion/beef soup. Anticancer activity of 8‐ CEPQ was evaluated by using cell viability assay and flow cytometry. Results showed that 8‐ CEPQ suppressed proliferation and caused G 2 phase arrest in colon cancer cells. Based on immunofluorescent staining assay, western blot assay, and RNA knockdown data, we found that 8‐ CEPQ did not cause apoptotic cell death. Instead, it induced autophagic cell death. Moreover, treatment with 8‐ CEPQ induced phosphorylation of extracellular signal‐regulated kinase (ERK). Inhibition of ERK phosphorylation by the mitogen‐activated protein kinase kinase (MEK)/ERK inhibitor U0126 attenuated 8‐ CEPQ ‐induced autophagy and reversed 8‐ CEPQ ‐mediated cell growth inhibition. Conclusion Our results demonstrate that 8‐ CEPQ , a novel quercetin derivative, could be formed in onion/beef soup. 8‐ CEPQ inhibited colon cancer cell growth by inducing autophagic cell death through ERK activation.