Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T lymphocytes, and breast cancer cells.
Paclitaxel or Taxol has attracted a great deal of attention in recent years because of its immense success as a chemotherapeutic agent for numerous types of cancer. It is known that paclitaxel stabilizes microtubules, and this characteristic is the presumed primary mechanism for its antitumor activity. Recently, however, paclitaxel's ability to regulate gene expression, particularly in the murine system, has been reported by several groups. Here, we present research examining paclitaxel's ability to alter expression of the interleukin-1beta (IL-1beta) and IL-8 cytokines in primary human monocytes, T lymphocytes, and four human breast cancer cell lines: MCF-7, ZR-75-1, MDA-MB-468, and MDA-MB-231. This report shows for the first time that treatment with 5-50 microM paclitaxel increases steady-state levels of IL-1beta mRNA in unprimed human monocytes, MCF-7, and ZR-75-1 cells. Monocytes from eight donors in 16 experiments showed increased IL-1beta secretion upon treatment; however, the increase in IL-1beta production by monocytes was predicated on culturing in the absence of fetal bovine serum or in the presence of autologous human serum. In contrast to the IL-1beta results, paclitaxel did not have significant effects on IL-8 expression by monocytes, T lymphocytes, or the breast cancer cells. These data show a specific effect of paclitaxel on cytokine synthesis by both immune cells and cancer cells.
White
C M
CM
University of North Carolina at Chapel Hill, School of Medicine, Department of Microbiology and Immunology, 27599-7295, USA.
Martin
B K
BK
Lee
L F
LF
Haskill
J S
JS
Ting
J P
JP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D017239:Paclitaxel