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Kaempferol inhibits cell proliferation and glycolysis in esophagus squamous cell carcinoma via targeting EGFR signaling pathway.
- Source :
-
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine [Tumour Biol] 2016 Aug; Vol. 37 (8), pp. 10247-56. Date of Electronic Publication: 2016 Feb 01. - Publication Year :
- 2016
-
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.
- Subjects :
- Animals
Blotting, Western
Carcinoma, Squamous Cell metabolism
Cell Line, Tumor
Esophageal Neoplasms metabolism
Esophageal Squamous Cell Carcinoma
Female
Flow Cytometry
Humans
Immunohistochemistry
Mice
Mice, Inbred BALB C
Signal Transduction drug effects
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Carcinoma, Squamous Cell pathology
Cell Proliferation drug effects
ErbB Receptors metabolism
Esophageal Neoplasms pathology
Glycolysis drug effects
Kaempferols pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0380
- Volume :
- 37
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 26831667
- Full Text :
- https://doi.org/10.1007/s13277-016-4912-6