Sequence dependence of the hyperthermic potentiation of carboplatin-induced cytotoxicity and intracellular platinum acumulation in HeLa cells

T. Kusumoto, Y. Maehara, H. Baba, I. Takahashi, H. Kusumoto, S. Ohno, K. Sugimachi

研究成果: ジャーナルへの寄稿学術誌査読

18 被引用数 (Scopus)

抄録

We have examined the enhancement of cytotoxic effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (carboplatin) by hyperthermia in HeLa cells using different regimes of timing and sequence. The results were compared with those obtained with cis-diamminedichloroplatinum(II) (cisplatin). We found that cisplatin simultaneously combined with heat was the most cytotoxic toward HeLa cells of the various timing and sequencing conditions studied. On the other hand, for carboplatin, drug treatment immediately following or during heat exposure showed the greatest effect. Intracellular platinum concentration in HeLa cells treated with heat before carboplatin showed a 2.75-fold increase over that in cells treated with the drug alone. The ratios for carboplatin given before, or during heating, were 0.67 and 1.42 respectively. Simultaneous exposure of cells to cisplatin and heat led to a 1.64-fold enhancement in cisplatin accumulation, compared to 0.92- and 1.24-fold increase for cells treated with cisplatin before and after heat respectively. Although each drug exposure prior to heat was less cytotoxic toward HeLa cells than any other heat/drug combination sequences, the platinum concentration was less than seen with each drug alone. Even though heat exposure prior to and during carboplatin showed a similar toxicity, platinum concentration in cells treated with heat prior to carboplatin was higher than that in cells treated with heat and carboplatin simultaneously. Thus, increased cytotoxicity cannot always be explained on the basis of intracellular platinum concentration. It is clear however that, differing from cisplatin, exposure of cells to heat prior to or during carboplatin administration results in the greatest cell kill.

本文言語英語
ページ(範囲)259-263
ページ数5
ジャーナルBritish journal of cancer
68
2
DOI
出版ステータス出版済み - 8月 1993

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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