Oncotarget

Research Papers:

Nitidine chloride acts as an apoptosis inducer in human oral cancer cells and a nude mouse xenograft model via inhibition of STAT3

Lee-Han Kim, Sachita Khadka, Ji-Ae Shin, Ji-Youn Jung, Mi-Heon Ryu, Hyun-Ju Yu, Hae Nim Lee, Boonsil Jang, In-Hyoung Yang, Dong-Hoon Won, Hye-Jeong Kwon, Joseph H. Jeong, Seong Doo Hong, Nam-Pyo Cho and Sung-Dae Cho _

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Oncotarget. 2017; 8:91306-91315. https://doi.org/10.18632/oncotarget.20444

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Abstract

Lee-Han Kim1,*, Sachita Khadka1,*, Ji-Ae Shin2, Ji-Youn Jung3, Mi-Heon Ryu4, Hyun-Ju Yu1, Hae Nim Lee3, Boonsil Jang1, In-Hyoung Yang1, Dong-Hoon Won2, Hye-Jeong Kwon2, Joseph H. Jeong5, Seong Doo Hong2, Nam-Pyo Cho1 and Sung-Dae Cho2

1Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju, 54896, Republic of Korea

2Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea

3Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, 32439, Republic of Korea

4Department of Oral Pathology, School of Dentistry, Yangsan Campus of Pusan National University, Yangsan, 50612, Republic of Korea

5Department of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University and Korea Mouse Phenotyping Center, Seoul, 08826, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Sung-Dae Cho, email: efiwdsc@snu.ac.kr

Nam-Pyo Cho, email: npcho@chonbuk.ac.kr

Keywords: nitidine chloride, oral cancer, apoptosis, STAT3

Received: April 21, 2017    Accepted: July 26, 2017    Published: August 24, 2017

ABSTRACT

Nitidine chloride (NC) is a natural alkaloid compound derived from the plant Zanthoxylum nitidum and is known for its therapeutic anticancer potential. In this study, we investigated the effects of NC on growth and signaling pathways in human oral cancer cell lines and a tumor xenograft model. The apoptotic effects and related molecular targets of NC on human oral cancer were investigated using trypan blue exclusion assay, DAPI staining, Live/Dead assay, Western blotting, Immunohistochemistry/Immunofluorescence and a nude mouse tumor xenograft. NC decreased cell viability in both HSC3 and HSC4 cell lines; further analysis demonstrated that cell viability was reduced via apoptosis. STAT3 was hyper-phosphorylated in human oral squamous cell carcinoma (OSCC) compared with normal oral mucosa (NOM) and dephosphorylation of STAT3 by the potent STAT3 inhibitor, cryptotanshinone or NC decreased cell viability and induced apoptosis. NC also suppressed cell viability and induced apoptosis accompanied by dephosphorylating STAT3 in four other oral cancer cell lines. In a tumor xenograft model bearing HSC3 cell tumors, NC suppressed tumor growth and induced apoptosis by regulating STAT3 signaling without liver or kidney toxicity. Our findings suggest that NC is a promising chemotherapeutic candidate against human oral cancer.


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