alexa Constitutive Activation of Caspase-3 in Non-Apoptotic Oral Squamous Cell Carcinoma Cells | OMICS International | Abstract
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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Research Article

Constitutive Activation of Caspase-3 in Non-Apoptotic Oral Squamous Cell Carcinoma Cells

Wataru Heshiki1, Kei Tomihara1*, Manabu Yamazaki2, Naoya Arai3, Kenji Nakamori1 and Makoto Noguchi1

1Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama 2630 Sugitani, Toyama City, Japan

2Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University, Graduate School of Medical and Dental Sciences, Niigata City, Japan

3Department of Oral and Maxillofacial Surgery, Division of Reparative and Regenerative Medicine, Institute of Medical Science, Mie University Graduate School of Medicine, Tsu, Mie, Japan

*Corresponding Author:
Kei Tomihara, DDS, PhD
Department of Oral and Maxillofacial Surgery
Graduate School of Medicine and Pharmaceutical Sciences for Research
University of Toyama, 2630 Sugitani
Toyama city, Toyama 930-0194, Japan
Tel: +81-76-434-7383 (ex 7383)
E-mail: [email protected]

Received date: December 03, 2014; Accepted date: February 12, 2015; Published date: February 28, 2015

Citation: Heshiki W, Tomihara K, Yamazaki M, Arai N, Nakamori K, et al. (2015) Constitutive Activation of Caspase-3 in Non-Apoptotic Oral Squamous Cell Carcinoma Cells. J Cancer Sci Ther 7: 075-080. doi:10.4172/1948-5956.1000328

Copyright: © 2015 Heshiki W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Although caspase-3 is a key molecule for apoptosis induction, recent evidence has suggested its protumoral role in various human malignancies. The aim of the present study was to investigate the expression of cleaved caspase-3 (the active form of caspase-3) in both clinical samples and cell lines from oral squamous cell carcinomas (OSCCs) and elaborate on its contribution to the protumor role in oral cancer.

Methods: The expression of cleaved caspase-3 was immunohistochemically evaluated in samples from 30 patients with OSCCs. The samples were either from biopsies or surgically-resected specimens with a mix of clinical stages and tumor site origins. The expression of cleaved caspase-3 was further examined in three OSCC cell lines.

Results: In addition to apoptotic cancer cells, all the cases of OSCCs demonstrated a surprisingly positive expression of cleaved caspase-3. A diffuse, cytoplasmic pattern was particularly prominent in in situ carcinoma cells, invasive carcinoma cells, and metastatic cancer cells that lacked apoptotic morphology. On the other hand, non-neoplastic, normal epithelial cells were completely negative for cleaved caspase-3. In all the OSCC cell lines studied, cleaved caspase-3 was expressed in the cytoplasm and nucleus of cancer cells. Flow cytometric analysis also confirmed that the activation level of caspase-3 in non-apoptotic cancer cells was relatively lower than that in apoptotic cancer cells. Moreover, caspase-3 inhibition by caspase-3 specific inhibitor decreased the proliferation of OSCC cells.

Conclusions: Because cleaved caspase-3 is selectively expressed in non-apoptotic OSCC cells and is associated with cell proliferation, these findings implicate caspase-3 signaling in promoting the progression of oral cancer.


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