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Cellular Oncology
Published in: Cellular Oncology 2/2014

01-04-2014 | Original Paper

Combined arsenic trioxide-cisplatin treatment enhances apoptosis in oral squamous cell carcinoma cells

Authors: Toshiki Nakaoka, Akinobu Ota, Takayuki Ono, Sivasundaram Karnan, Hiroyuki Konishi, Akifumi Furuhashi, Yukinobu Ohmura, Yoichi Yamada, Yoshitaka Hosokawa, Yoshiaki Kazaoka

Published in: Cellular Oncology | Issue 2/2014

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Abstract

Background

Oral squamous cell carcinoma (OSCC) accounts for the majority of oral cancers. Despite recent advances in OSCC diagnostics and therapeutics, the overall survival rate still remains low. Here, we assessed the efficacy of a combinatorial arsenic trioxide (ATO) and cisplatin (CDDP) treatment in human OSCC cells.

Methods

The combinatorial effect of ATO/CDDP on the growth and apoptosis of OSCC cell lines HSC-2, HSC-3, and HSC-4 was evaluated using MTT and annexin V assays, respectively. Chou–Talalay analyses were preformed to evaluate the combinatorial effects of ATO/CDDP on the dose-reduction index (DRI). To clarify the mechanism underlying the ATO/CDDP anticancer effect, we also examined the involvement of reactive oxygen species (ROS) in ATO/CDDP-induced apoptosis.

Results

Combination index (CI) analyses revealed that a synergistic interaction of ATO and CDDP elicits a wide range of effects in HSC-2 cells, with CI values ranging from 0.78 to 0.90, where CI < 1 defines synergism. The CI values in HSC-3 and HSC-4 cells ranged from 0.34 to 0.45 and from 0.60 to 0.92, respectively. In addition, ATO/CDDP yielded favorable DRI values ranging from 1.6-fold to 7.71-fold dose reduction. Compared to mono-therapy, ATO/CDDP combinatorial therapy significantly augmented the loss of mitochondrial potential, caspase-3/7 activity and subsequent apoptosis. These changes were all abrogated by the antioxidant N-acetylcysteine.

Conclusions

This study provides the first evidence for a synergistic ATO/CDDP anticancer (apoptotic) activity in OSCC cells with a favorable DRI, thereby highlighting its potential as a combinational therapeutic regime in OSCC.
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Metadata
Title
Combined arsenic trioxide-cisplatin treatment enhances apoptosis in oral squamous cell carcinoma cells
Authors
Toshiki Nakaoka
Akinobu Ota
Takayuki Ono
Sivasundaram Karnan
Hiroyuki Konishi
Akifumi Furuhashi
Yukinobu Ohmura
Yoichi Yamada
Yoshitaka Hosokawa
Yoshiaki Kazaoka
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 2/2014
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-014-0167-7

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