title: Kaempferol inhibits cell proliferation and glycolysis in esophagus squamous cell carcinoma via targeting EGFR signaling pathway.
abstract: Antitumor activity of kaempferol has been studied in various tumor types, but its potency in esophagus squamous cell carcinoma is rarely known. Here, we reported the activity of kaempferol against esophagus squamous cell carcinoma as well as its antitumor mechanisms. Results of cell proliferation and colony formation assay showed that kaempferol substantially inhibited tumor cell proliferation and clone formation in vitro. Flow cytometric analysis demonstrated that tumor cells were induced G0/G1 phase arrest after kaempferol treatment, and the expression of protein involved in cell cycle regulation was dramatically changed. Except the potency on cell proliferation, we also discovered that kaempferol had a significant inhibitory effect against tumor glycolysis. With the downregulation of hexokinase-2, glucose uptake and lactate production in tumor cells were dramatically declined. Mechanism studies revealed kaempferol had a direct effect on epidermal growth factor receptor (EGFR) activity, and along with the inhibition of EGFR, its downstream signaling pathways were also markedly suppressed. Further investigations found that exogenous overexpression of EGFR in tumor cells substantially attenuated glycolysis suppression induced by kaempferol, which implied that EGFR also played an important role in kaempferol-mediated glycolysis inhibition. Finally, the antitumor activity of kaempferol was validated in xenograft model and kaempferol prominently restrained tumor growth in vivo. Meanwhile, dramatic decrease of EGFR activity and hexokinase-2 expression were observed in kaempferol-treated tumor tissue, which confirmed these findings in vitro. Briefly, these studies suggested that kaempferol, or its analogues, may serve as effective candidates for esophagus squamous cell carcinoma management.
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, No. 241 West Huaihai Road, Shanghai, 200030, China.|Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, No. 241 West Huaihai Road, Shanghai, 200030, China. vwtfang@hotmail.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Fang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005434:Flow Cytometry; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D044949:Kaempferols / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D044949:Kaempferols; C006552:kaempferol; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Esophagus squamous cell carcinoma; Glycolysis; Hexokinase-2; Kaempferol
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