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Regression of Human Breast Carcinoma Tumors in Immunodeficient Mice Treated with 9-Nitrocamptothecin: Differential Response of Nontumorigenic and Tumorigenic Human Breast Cells in Vitro¹

The Stehlin Foundation for Cancer Research and St. Joseph Hospital Cancer Laboratory, Houston, Texas 77003

We have shown recently that the plant alkaloid camptothecin and its derivatives inhibited growth of human carcinoma and melanoma cells in vitro and induced regression of advanced human malignant melanoma tumors growing in immunodeficient (nude) mice. Here, we have extended these studies to show that the camptothecin derivative 9-nitro-20(S)-camptothecin (9NC) induces complete regression of advanced breast carcinoma tumors growing in nude mice. We also report that 9NC inhibits growth of nontumorigenic and tumorigenic breast cells in vitro. However, flow cytometry studies show that 9NC elicits differential effects on the cell cycle of nontumorigenic and tumorigenic cells. In general, 9NC-treated nontumorigenic cells accumulate slowly at the G₂ phase of the cell cycle with no cell death. In contrast, 9NC-treated tumorigenic cells traverse rapidly from G₁ to S phase followed by cell death. Removal of 9NC from the cell cultures resulted in most nontumorigenic cells dividing, whereas tumorigenic cells continued to die after removal of 9NC. Taken together, the findings indicate a different response of nontumorigenic and tumorigenic breast cells to 9NC.

¹ This work was supported by funds from The Stehlin Foundation for Cancer Research and The Friends of The Stehlin Foundation.

² To whom requests for reprints should be addressed, at The Stehlin Foundation for Cancer Research and St. Joseph Hospital Cancer Laboratory, 1918 Chenevert Street, Houston, TX 77003.

Received 9/11/92. Accepted 1/20/93.

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