In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines

Risa Tanaka, Yasushi Takii, Yoshihiro Shibata, hiroshi ariyama, Baoli Qin, Eishi Baba, Hitoshi Kusaba, Kenji Mitsugi, Mine Harada, Shuji Nakano

Research output: Contribution to journalArticle

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Abstract

Purpose: To define the most effective combination schedule of paclitaxel and nedaplatin, a new platinum derivative, we investigated the in vitro interaction between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1 esophageal squamous carcinoma cell lines. Materials and methods: Cytotoxic activity was determined by the WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism using a quantitative method based on the median-effect principle of Chou and Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow cytometry. Results: Upon 24-h sequential exposure, the sequence paclitaxel followed by nedaplatin induced greater than additive effects in all of the cell lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast, antagonistic effects were observed with the reverse sequence. Simultaneous treatment resulted in either a synergistic or antagonistic effect, depending on the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears most active, at least in these three cell lines. Flow cytometric analyses at IC50 indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis (56%) in the sub-G1 phase. When paclitaxel preceded nedaplatin, apoptosis was most prominent (70%) with pronounced G2/M arrest. By contrast, the reverse sequence yielded only 28% induction of apoptotic cells, with almost identical cell-cycle distribution patterns to those observed with nedaplatin alone, indicating that the activity of paclitaxel is abolished by pretreatment with nedaplatin. Conclusions: Our findings suggest that the interaction of nedaplatin and paclitaxel is highly schedule dependent and that the sequential administration of paclitaxel followed by nedaplatin should be thus incorporated into the design of a clinical trial.

Original languageEnglish
Pages (from-to)279-285
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume56
Issue number3
DOIs
Publication statusPublished - Sep 1 2005

Fingerprint

Paclitaxel
Cells
Cell Line
Neoplasms
Appointments and Schedules
Apoptosis
Cell Cycle
Flow cytometry
nedaplatin
In Vitro Techniques
G1 Phase
Platinum
Drug Interactions
Pharmaceutical Preparations
Inhibitory Concentration 50
Squamous Cell Carcinoma
Assays
Stomach
Flow Cytometry
Adenocarcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines. / Tanaka, Risa; Takii, Yasushi; Shibata, Yoshihiro; ariyama, hiroshi; Qin, Baoli; Baba, Eishi; Kusaba, Hitoshi; Mitsugi, Kenji; Harada, Mine; Nakano, Shuji.

In: Cancer Chemotherapy and Pharmacology, Vol. 56, No. 3, 01.09.2005, p. 279-285.

Research output: Contribution to journalArticle

Tanaka, Risa ; Takii, Yasushi ; Shibata, Yoshihiro ; ariyama, hiroshi ; Qin, Baoli ; Baba, Eishi ; Kusaba, Hitoshi ; Mitsugi, Kenji ; Harada, Mine ; Nakano, Shuji. / In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines. In: Cancer Chemotherapy and Pharmacology. 2005 ; Vol. 56, No. 3. pp. 279-285.
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abstract = "Purpose: To define the most effective combination schedule of paclitaxel and nedaplatin, a new platinum derivative, we investigated the in vitro interaction between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1 esophageal squamous carcinoma cell lines. Materials and methods: Cytotoxic activity was determined by the WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism using a quantitative method based on the median-effect principle of Chou and Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow cytometry. Results: Upon 24-h sequential exposure, the sequence paclitaxel followed by nedaplatin induced greater than additive effects in all of the cell lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast, antagonistic effects were observed with the reverse sequence. Simultaneous treatment resulted in either a synergistic or antagonistic effect, depending on the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears most active, at least in these three cell lines. Flow cytometric analyses at IC50 indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis (56{\%}) in the sub-G1 phase. When paclitaxel preceded nedaplatin, apoptosis was most prominent (70{\%}) with pronounced G2/M arrest. By contrast, the reverse sequence yielded only 28{\%} induction of apoptotic cells, with almost identical cell-cycle distribution patterns to those observed with nedaplatin alone, indicating that the activity of paclitaxel is abolished by pretreatment with nedaplatin. Conclusions: Our findings suggest that the interaction of nedaplatin and paclitaxel is highly schedule dependent and that the sequential administration of paclitaxel followed by nedaplatin should be thus incorporated into the design of a clinical trial.",
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T1 - In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines

AU - Tanaka, Risa

AU - Takii, Yasushi

AU - Shibata, Yoshihiro

AU - ariyama, hiroshi

AU - Qin, Baoli

AU - Baba, Eishi

AU - Kusaba, Hitoshi

AU - Mitsugi, Kenji

AU - Harada, Mine

AU - Nakano, Shuji

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Purpose: To define the most effective combination schedule of paclitaxel and nedaplatin, a new platinum derivative, we investigated the in vitro interaction between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1 esophageal squamous carcinoma cell lines. Materials and methods: Cytotoxic activity was determined by the WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism using a quantitative method based on the median-effect principle of Chou and Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow cytometry. Results: Upon 24-h sequential exposure, the sequence paclitaxel followed by nedaplatin induced greater than additive effects in all of the cell lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast, antagonistic effects were observed with the reverse sequence. Simultaneous treatment resulted in either a synergistic or antagonistic effect, depending on the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears most active, at least in these three cell lines. Flow cytometric analyses at IC50 indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis (56%) in the sub-G1 phase. When paclitaxel preceded nedaplatin, apoptosis was most prominent (70%) with pronounced G2/M arrest. By contrast, the reverse sequence yielded only 28% induction of apoptotic cells, with almost identical cell-cycle distribution patterns to those observed with nedaplatin alone, indicating that the activity of paclitaxel is abolished by pretreatment with nedaplatin. Conclusions: Our findings suggest that the interaction of nedaplatin and paclitaxel is highly schedule dependent and that the sequential administration of paclitaxel followed by nedaplatin should be thus incorporated into the design of a clinical trial.

AB - Purpose: To define the most effective combination schedule of paclitaxel and nedaplatin, a new platinum derivative, we investigated the in vitro interaction between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1 esophageal squamous carcinoma cell lines. Materials and methods: Cytotoxic activity was determined by the WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism using a quantitative method based on the median-effect principle of Chou and Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow cytometry. Results: Upon 24-h sequential exposure, the sequence paclitaxel followed by nedaplatin induced greater than additive effects in all of the cell lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast, antagonistic effects were observed with the reverse sequence. Simultaneous treatment resulted in either a synergistic or antagonistic effect, depending on the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears most active, at least in these three cell lines. Flow cytometric analyses at IC50 indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis (56%) in the sub-G1 phase. When paclitaxel preceded nedaplatin, apoptosis was most prominent (70%) with pronounced G2/M arrest. By contrast, the reverse sequence yielded only 28% induction of apoptotic cells, with almost identical cell-cycle distribution patterns to those observed with nedaplatin alone, indicating that the activity of paclitaxel is abolished by pretreatment with nedaplatin. Conclusions: Our findings suggest that the interaction of nedaplatin and paclitaxel is highly schedule dependent and that the sequential administration of paclitaxel followed by nedaplatin should be thus incorporated into the design of a clinical trial.

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