Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs.
Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1beta and TNF-alpha). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action.
Calatayud
S
S
Unit of Critical Care, The Royal Brompton and Harefield N.H.S. Trust, Imperial College School of Medicine, Sydney Street, London SW3 6NP, UK. sara.calatayud@uv.es
Warner
T D
TD
Mitchell
J A
JA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003115:Colony-Stimulating Factors; D016207:Cytokines; D003513:Cycloheximide