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The use of human cancer cell lines as a primary screening system for antineoplastic compounds
Abstract:
Exponentially growing cells of human cancer lines have been utilized to investigate the cytotoxic activity of antineoplastic agents. Different cancer cell lines differ greatly in their responsiveness to both clinical and experimental cytotoxic drugs. For example, sensitivities to 5-fluorouracil and cytosine arabinoside ranged over 15- and 30-fold respectively. Cell lines derived from carcinomas were more sensitive to 5-fluorouracil and less sensitive to cytosine arabinoside than was a leukaemic cell line. In general, colon carcinoma lines were most resistant to DNA-intercalating drugs, and a breast carcinoma and leukaemia line most sensitive. In a congeneric series of amsacrine analogues, in vitro patterns of activity against different lines were shown to correlate with activity against the Lewis lung mouse carcinoma in vivo. Results suggest that established cell lines manifest responsiveness to anticancer drugs consistent with that expected from their tumours of origin. This assay is economical, reproducible and convenient, and could be used to complement the human tumour stem cell assay in drug development studies.
Insights
Human cancer cell lines show varied responses to anticancer drugs, mirroring their tumor origins. This reproducible assay aids in developing new cancer therapies by predicting drug effectiveness.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Human cancer cell lines are vital for studying cytotoxic antineoplastic agents.
- Significant variability exists in cancer cell line sensitivity to various cytotoxic drugs.
- Drug sensitivity can differ based on the cancer cell line's origin (e.g., carcinoma vs. leukemia).
Purpose of the Study:
- To investigate the cytotoxic activity of antineoplastic agents using exponentially growing human cancer cell lines.
- To determine if in vitro drug sensitivity patterns correlate with in vivo tumor responses.
- To evaluate the utility of established cell lines as a model for predicting anticancer drug efficacy.
Main Methods:
- Utilized exponentially growing human cancer cell lines to test cytotoxic activity of antineoplastic agents.
- Assessed differential sensitivities to drugs like 5-fluorouracil and cytosine arabinoside across various cell lines.
- Correlated in vitro activity of amsacrine analogues with in vivo activity against Lewis lung mouse carcinoma.
Main Results:
- Demonstrated a 15-fold range in sensitivity to 5-fluorouracil and a 30-fold range to cytosine arabinoside.
- Carcinoma cell lines showed higher sensitivity to 5-fluorouracil and lower sensitivity to cytosine arabinoside compared to a leukemia cell line.
- Established cell lines exhibited drug responsiveness consistent with their tumors of origin, with colon carcinoma lines being most resistant to DNA-intercalating drugs.
Conclusions:
- Established human cancer cell lines can predict anticancer drug responsiveness based on tumor origin.
- The cell line assay is economical, reproducible, and convenient for drug development.
- This assay can complement existing methods like the human tumor stem cell assay in preclinical drug studies.