8-C-(E-phenylethenyl)quercetin from onion/beef soup induces autophagic cell death in colon cancer cells through ERK activation.
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.



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 G2phase 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.



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.
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Yueliang
Y
Zhao
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Daming
D
Fan
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Zong-Ping
ZP
Zheng
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Edmund T S
ET
Li
College of Engineering, Institute for Food & Bioresource Engineering, Peking University, Beijing, China.
Feng
F
Chen
College of Engineering, Institute for Food & Bioresource Engineering, Peking University, Beijing, China.
Ka-Wing
KW
Cheng
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Mingfu
M
Wang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003296:Cooking; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D019697:Onions; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D000069466:Red Meat
C000625633:8-C-(phenylethenyl)quercetin; D000970:Antineoplastic Agents; D011794:Quercetin; D048049:Extracellular Signal-Regulated MAP Kinases
8-C-(E-phenylethenyl)quercetin; Autophagy; Colon cancer; ERK activation; Onion/beef soup