Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity

Shuai Jiang, Amy W. Pan, Tzu-Yin Lin, Hongyong Zhang, Michael Malfatti, Ken W Turteltaub, Paul Henderson, Chong-Xian Pan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

This rapid report focuses on the pharmacodynamic mechanism of the carboplatin/paclitaxel combination and correlates it with its cytotoxicity. Consistent with the synergistic to additive antitumor activity (the combination index ranging from 0.53 to 0.94), cells exposed to this combination had significantly increased carboplatin-DNA adduct formation when compared to that of carboplatin alone (450 ± 30 versus 320 ± 120 adducts per 108 nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 108 nucleotides per hour in carboplatin alone (p = 0.021). This rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.

Original languageEnglish (US)
Pages (from-to)2250-2252
Number of pages3
JournalChemical Research in Toxicology
Volume28
Issue number12
DOIs
StatePublished - Dec 21 2015

ASJC Scopus subject areas

  • Toxicology

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