Chemical and biological stability of anticancer drugs used in a human tumor clonogenic assay

Ruth Ludwig, David S Alberts

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Human tumor clonogenic assays (HTCA) are being used to evaluate the chemosensitivity of human cancers to both standard and experimental anticancer drugs as well as to predict clinical tumor response and resistance to these agents. To enable us to design and accurately interpret drug assay data we quantitated the chemical and biological stability characteristics of various cell cycle-specific and cell cyle-nonspecific drugs commonly used in our laboratory for chemosensitivity testing in the HTCA. Aliquots of the culture media were obtained immediately after drug addition and after 6 and 24 h and 2, 4, and 10 days of incubation, and then frozen in liquid nitrogen for later chemical (HPLC or RIA) and biological (HTCA) assay. Adriamycin, actinomycin D, bisantrene, bleomycin, and vinblastine retained 80-100% of their biological activity against human tumor colony-forming units even after 10 days of incubation in culture media. In contrast, etoposide lost 60% of its in vitro antitumor activity over the same period. There was no loss in the chemical concentration of actinomycin D. bisantrene, bleomycin, or vinblastine in the culture media, but etoposide concentrations as measured by HPLC decreased to zero over 10 days. We conclude that the HTCA can be used as a simple test for biological stability of new investigational agents prior to the development of adequate chemical assay methodology, and that it can help clarify whether a drug's in vitro antitumor activity is due to the parent compound or to a degradation products.

Original languageEnglish (US)
Pages (from-to)142-145
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume12
Issue number3
DOIs
StatePublished - Apr 1984

Fingerprint

Drug Stability
Tumors
Assays
bisantrene
Pharmaceutical Preparations
Neoplasms
Culture Media
Vinblastine
Bleomycin
Dactinomycin
Etoposide
High Pressure Liquid Chromatography
Liquid nitrogen
Bioactivity
Human Activities
Doxorubicin
Cell Cycle
Nitrogen
Stem Cells
Cells

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Chemical and biological stability of anticancer drugs used in a human tumor clonogenic assay. / Ludwig, Ruth; Alberts, David S.

In: Cancer Chemotherapy and Pharmacology, Vol. 12, No. 3, 04.1984, p. 142-145.

Research output: Contribution to journalArticle

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