Combinations of recombinant interferon alfa2 (IFN-α2) with doxorubicin, 4′-epidoxorubicin, 4′-deoxydoxorubicin, or 4-demethoxydaunorubicin were tested for antiproliferative activity against a panel of human tumor cell lines in a human tumor clonogenic assay. The histologies of the cell lines were ovary, cervix, breast, and melanoma. Each of the cytotoxic compounds showed dose-dependent antiproliferative effects against each of the cell lines, and the results indicated that doxorubicin derivatives were consistently more potent than the parent drug. In all instances, 4-demethoxydaunorubicin was the most potent derivative, requiring 2–20 times less drug to inhibit 70% of tumor colony formation. Combinations of IFN-α2, with doxorubicin or its derivatives may show additive or synergistic antiproliferative activity against certain tumor cell lines. The ovarian carcinoma cell line, BG-1, responded synergistically to each of the four compounds in combination with IFN-α2. The cervical carcinoma cell line, CaSki, and the breast carcinoma line, MCF-7, responded to the combinations in a manner best described as additive. In the melanoma line, SK-Mel-28, the drugs were found to be subadditive or even antagonistic. While the potency of the anthracyline derivatives ranked consistently across the different cell lines, the synergistic interaction with IFN-α2 is a cell line-specific phenomenon unrelated to sensitivity to either anthracyclines or interferon.
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Supported by a grant from Farmitalia Carlo Erba, Milan, Italy
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Berens, M.E., Saito, T., Welander, C.E. et al. Antitumor activity of new anthracycline analogues in combination with interferon alfa. Cancer Chemother. Pharmacol. 19, 301–306 (1987). https://doi.org/10.1007/BF00261477
- Carcinoma Cell Line
- Ovarian Carcinoma
- Human Tumor Cell Line