title: Icaritin Reduces Oral Squamous Cell Carcinoma Progression via the Inhibition of STAT3 Signaling.
abstract: Icaritin, a traditional Chinese medicine, possesses antitumor activity. The current study aimed to investigate icaritin effect and potential mechanism on oral squamous cell carcinoma (OSCC) development. OSCC cells proliferation, apoptosis, and autophagy were analyzed after incubation with icaritin at different concentrations and incubation times. The expressions of proteins related to proliferation, apoptosis, and autophagy, as well as signal transducer and activator of transcription 3 (STAT3) signal network, were also evaluated by western blot. Furthermore, STAT3 was knocked down by siRNA transfection to determine STAT3 role in OSCC cell proliferation and apoptosis. An oral specific carcinogenesis mouse model was used to explore icaritin effect on OSCC in vivo. Icaritin significantly inhibited OSCC proliferation in vitro and reduced the expression of both the cell-cycle progression proteins cyclin A2 and cyclin D1. Besides, icaritin increased cleaved caspase 3 and cleaved poly-(ADP-ribose) polymerase expression leading to apoptosis, and it activated autophagy. Icaritin significantly inhibited the expression of phospho-STAT3 (p-STAT3) in a dose- and time-dependent manner. In the in vivo experiment, the number of malignant tumors in the icaritin-treated group was significantly lower than the control. Overall, icaritin suppressed proliferation, promoted apoptosis and autophagy, and inhibited STAT3 signaling in OSCC in vitro and in vivo. In conclusion, icaritin might be a potential therapeutic agent against OSCC development.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. 2014103040017@whu.edu.cn.
authors.forename: Jian-Guang
authors.initials: JG
authors.lastname: Yang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. KQ000874@whu.edu.cn.|Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. KQ000874@whu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. 2014103040018@whu.edu.cn.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Ye
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. zhang_lin_ling@whu.edu.cn.|Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. zhang_lin_ling@whu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. 2015103040008@whu.edu.cn.
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Tan
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. gordonzhou@tom.com.|Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. gordonzhou@tom.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016213:Cyclins / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D016213:Cyclins; D005419:Flavonoids; D050796:STAT3 Transcription Factor; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C499403:icaritin
keywords: icaritin; oral squamous cell carcinoma; premalignant lesion; signal transducer and activator of transcription 3