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Published on: September 8, 2017
Cytotoxicity induced by docetaxel in human oral squamous cell carcinoma cell lines
Satori Iida1, Jun Shimada, Hiroshi Sakagami
1Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
Background:
Comparative studies of cytotoxicity of docetaxel against both oral normal and tumor cells are limited. In the present study, the cytotoxicity of docetaxel towards human oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3, HSC-4) and human oral normal cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) was investigated.
Materials And Methods:
The cytotoxicity was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. Apoptosis induction was monitored by caspase-3/7 activation, DNA fragmentation, and production of annexin-positive cells, and necrosis induction by production of propidium iodide-positive cells.
Results:
Docetaxel induced various apoptotic markers without loss of the mitochondrial membrane potential and then necrosis markers. When the cells were rinsed with serum-free medium, the cell viability of OSCCs significantly declined. Fetal bovine serum was then fractionated by stepwise ultrafiltration. The growth-promoting activity of fetal bovine serum was heat-stable, and recovered from the fraction >100 kDa. Rinsing with serum-free medium also enhanced the cytotoxicity of docetaxel.
Conclusion:
The present results suggest that docetaxel may induce apoptosis via a mitochondrial-independent pathway and rinsing of target cells or organs with serum-free medium may reduce the clinical dose of docetaxel and its side effects.
Insights
Docetaxel induces apoptosis and necrosis in oral cancer cells. Rinsing with serum-free medium enhances docetaxel cytotoxicity, potentially reducing clinical doses and side effects.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Limited comparative studies exist on docetaxel cytotoxicity in oral normal and tumor cells.
- This study investigates docetaxel's effects on human oral squamous cell carcinoma (OSCC) and normal oral cells.
Purpose of the Study:
- To compare the cytotoxicity of docetaxel against human oral squamous cell carcinoma (OSCC) cell lines and normal oral cells.
- To investigate the mechanisms of docetaxel-induced cell death, including apoptosis and necrosis.
- To explore the impact of serum-free medium on docetaxel's efficacy.
Main Methods:
- Cytotoxicity assessed using the 3-"[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide" (MTT) assay.
- Apoptosis markers (caspase-3/7 activation, DNA fragmentation, annexin V) and necrosis marker (propidium iodide) were monitored.
- Fetal bovine serum fractionation and cell rinsing with serum-free medium were performed.
Main Results:
- Docetaxel induced apoptosis via a mitochondrial-independent pathway, followed by necrosis.
- Cell viability of OSCCs significantly declined upon rinsing with serum-free medium.
- Rinsing with serum-free medium enhanced docetaxel's cytotoxicity.
Conclusions:
- Docetaxel may induce apoptosis through a mitochondrial-independent pathway.
- Rinsing with serum-free medium could reduce clinical docetaxel dosage and associated side effects.
- Findings suggest a potential strategy for optimizing docetaxel therapy in oral cancer.

