This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tan, Y. Y. Articles by Armstrong, R. D. Search for Related Content PubMed PubMed Citation Articles by Tan, Y. Y. Articles by Armstrong, R. D.

In Vitro Evaluation of 6-Thioguanine and -Interferon as a Therapeutic Combination in HL-60 and Natural Killer Cells¹

La Jolla Cancer Research Foundation, La Jolla, California 92037 [R. D. A.] and Cancer Research Institute [Y. Y. T., L. B. E., R. D. A.], and Department of Pediatrics [L. B. E.], University of California, San Francisco, California 94143

The effect of 6-thioguanine (6-TG) and -interferon (IFN-) was evaluated in vitro to determine their effectiveness in combination on the therapeutically relevant events of: HL-60 cell cytotoxicity, HL-60 cell differentiation, and natural killer (NK)-cell mediated cytotoxicity. 6-TG was toxic to HL-60 cells (ID₅₀ = 0.6 µM; 24-h exposure) while IFN- (up to 1000 IU/ml) had minimal cytotoxic activity. Sequence-dependent activity was observed, inasmuch as the IFN- pretreatment sequence was antagonistic, while the other schedules were additive or, possibly, synergistic. The combination of 0.5 µM 6-TG and 100 IU/ml IFN- produced the same level of HL-60 cell differentiation as each agent alone, suggesting no benefit from the combination on this process. The effect of 6-TG and IFN- on NK cell-mediated cytotoxicity was found to be sequence dependent. NK cell activity was markedly stimulated by IFN-, whereas 6-TG alone seemed to have no direct effect. However, when the NK cells were pretreated with 100 IU/ml IFN- followed by 10 µM 6-TG, the IFN--enhanced activity of NK cells was ablated. These results suggest that the immunosuppressive activity of 6-TG may be related to the acute inhibition of cytokine activation. Our results suggest that 6-TG and IFN- have considerable interactions, which are sequence dependent. The optimal sequence for potential therapeutic application of these anticancer agents appears to be 6-TG pretreatment followed by IFN-.

¹ These studies were supported by Grant CH-329 from the American Cancer Society and NIH Grant CA 27903.

² Dr. Yu Ying Tan was a visiting professor from the Cancer Research Institute, Harbin Medical University, The People's Republic of China.

³ To whom requests for reprints should be addressed, at the La Jolla Cancer Research Foundation, 10901 No. Torrey Pines Rd., La Jolla, CA 92037.

Received 8/22/88. Revised 11/29/88. Revised 5/ 8/89. Accepted 5/15/89.

This article has been cited by other articles:

				Y. Tan, X. Sun, M. Xu, X. Tan, A. Sasson, B. Rashidi, Q. Han, X. Tan, X. Wang, Z. An, et al. Efficacy of Recombinant Methioninase in Combination with Cisplatin on Human Colon Tumors in Nude Mice Clin. Cancer Res., August 1, 1999; 5(8): 2157 - 2163. [Abstract] [Full Text] [PDF]