Potentiation of induction of apoptosis by sequential treatment with cisplatin followed by 5-fluorouracil in human oral cancer cells

Azuma,Masayuki; Harada,Koji; Supriatno,; Tamatani,Tetsuya; Motegi,Katsumi; Ashida,Yuki; Sato,Mitsunobu

doi:10.3892/ijo.24.6.1449

June 2004 Volume 24 Issue 6

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June 2004 Volume 24 Issue 6

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Article

Potentiation of induction of apoptosis by sequential treatment with cisplatin followed by 5-fluorouracil in human oral cancer cells

Authors:
- Masayuki Azuma
- Koji Harada
- Supriatno
- Tetsuya Tamatani
- Katsumi Motegi
- Yuki Ashida
- Mitsunobu Sato
View Affiliations / Copyright

Affiliations: Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan. azumasa@dent.tokushima-u.ac.jp
Pages: 1449-1455
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Published online on: June 1, 2004

https://doi.org/10.3892/ijo.24.6.1449
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Abstract

We examined the mechanism involved in the induction of apoptosis in human oral cancer (B88) cells with 5-fluorouracil (5-FU) and cisplatin (CDDP) combination. Three different combination treatment sequences were evaluated: i) 5-FU administered simultaneously with CDDP for 72 h (sequence I); ii) CDDP administered for 24 h before 5-FU treatment for 48 h (sequence II); and iii) 5-FU administered for 24 h before CDDP treatment for 48 h (sequence III). When combining the two drugs at doses 40% of their respective cytotoxicity, the growth-suppressing ratios were 49, 55, and 40% in sequences I, II, and III, respectively. Caspase 3 was significantly activated in sequence II as compared to its level of activation in sequence I or III. The mitochondrial release of cytochrome c was much greater in sequence II than in sequence III. In addition, activation of caspase 8 was most strongly activated in sequence II as compared with sequences I and III. Activation of caspase-9 was also observed in sequence II, and, to a lesser extent, in sequence III. Finally, although Bcl-2 was reduced in sequence II, no significant change was observed in sequence III. Accordingly, the data presented here demonstrate that sequence II showing a significant increase in the induction of apoptosis of cancer cells, is superior to sequences I and III.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Potentiation of induction of apoptosis by sequential treatment with cisplatin followed by 5-fluorouracil in human oral cancer cells

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