title: Tannic acid inhibits the Jak2/STAT3 pathway and induces G1/S arrest and mitochondrial apoptosis in YD-38 gingival cancer cells.
abstract: Tannic acid (TA), is a potent anti-oxidant, showing anti-proliferative effects on numerous cancers. The ability of TA to induce proliferation inhibition on the rare tumor, gingival squamous cell carcinoma (GSCC), comprising <10% of all head and neck squamous cell carcinomas was studied in the YD-38 cell line. The main goal was to modulate the Jak2/STAT3 pathway using TA and to induce cell cycle arrest and apoptosis in GSCC. TA treatment induced G1 arrest and apoptosis in YD-38 cells. Molecular analysis revealed that TA inhibits Jak2/STAT3 pathway by preventing their expression as well as phosphorylation. This inhibition of STAT3 phosphorylation prevented the nuclear translocation and DNA binding capability of STAT3. Together with the inhibition of transcriptional regulatory function of STAT3, TA inhibited the expression of G1 phase modulators CDK-4, CDK-6, cyclin D1 and cyclin E. It is also evidenced that TA exerted an intense activation of p21Waf1/Cip1, p27Kip1 and p53 genes confirming its role in G1 phase inhibition. Additionally, upon treatment with TA, the expression of mitochondrial pore factors Bax, Bcl-2 and Bcl-XL were changed. We observed inhibition of Bcl-2 and an increase in mitochondrial localization of Bax leading to the loss of mitochondrial membrane potential, resulting in the release of cytochrome c to the cytosol. In addition, we perceived the activation of caspases upon TA treatment. Specific inhibition of caspase protected the cells from TA induced apoptosis. Taken together, this study reveals that TA significantly inhibits the Jak2/STAT3 signaling pathway and induces G1 arrest and mitochondrial apoptosis in YD-38 cells.
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Pramod
authors.initials: P
authors.lastname: Darvin
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Seung Jo
authors.initials: SJ
authors.lastname: Baeg
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Joung
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Nipin
authors.initials: N
authors.lastname: Sp
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kang
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyo Joo
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Je Uk
authors.initials: JU
authors.lastname: Park
authors.affiliation: Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005887:Gingival Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013634:Tannins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013634:Tannins; C507924:JAK2 protein, human; D053614:Janus Kinase 2