Abstract | BACKGROUND: 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.
|
Authors | Toshiki Nakaoka, Akinobu Ota, Takayuki Ono, Sivasundaram Karnan, Hiroyuki Konishi, Akifumi Furuhashi, Yukinobu Ohmura, Yoichi Yamada, Yoshitaka Hosokawa, Yoshiaki Kazaoka |
Journal | Cellular oncology (Dordrecht)
(Cell Oncol (Dordr))
Vol. 37
Issue 2
Pg. 119-29
(Apr 2014)
ISSN: 2211-3436 [Electronic] Netherlands |
PMID | 24599717
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents
- Arsenicals
- Oxides
- Reactive Oxygen Species
- Cisplatin
- Arsenic Trioxide
|
Topics |
- Antineoplastic Agents
(therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(pharmacology)
- Carcinoma, Squamous Cell
(drug therapy, pathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cisplatin
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Synergism
- Humans
- Membrane Potential, Mitochondrial
(drug effects)
- Mouth Neoplasms
(drug therapy, pathology)
- Oxides
(pharmacology)
- Reactive Oxygen Species
(metabolism)
|